Virginia Institute for Psychiatric and Behavioral Genetics
www.vipbg.vcu.edu July 2004-June 2005
Kenneth S. Kendler, M.D., Co-Director
Table of Contents
Executive Summary 2
About VCU 3
VIPBG Faculty and Staff 7
Major Areas of Research 10
Major Accomplishments 13
VIPBG Publications 15
Active Research Grants 19
Budget Breakdown 24
for 2005-2006 25
Lindon J. Eaves, Ph.D., Co-Director Michael C. Neale, Ph.D., Associate Director
(804) 828-8155 (804) 828-3369
Psychiatric and Behavioral
Virginia Commonwealth University
800 E. Leigh Street, P.O. Box 980126
Richmond, VA 23298-0126
From the Directors
Psychiatric disorders are among the most frequent, distressing and poor-
ly understood human disorders. Schizophrenia, autism, depression, anti-social
behavior, ADHD, substance abuse, alcoholism: the list is long and the conse-
quences often devastating.
The VIPBG was founded eight years ago in the conviction that the com-
plexities of human behavior and its disorders would yield better to a community
of minds than a loose collection of scattered individualists. Forty years ago, one
person could know all there was to know about Genetics. The same solitary
geneticist might count hairs on fruit-flies one day and draw the chromosomes of
an onion the next. These days, it helps to have company. No longer is it possible Lindon J. Eaves
for any one individual - despite his or her level of brilliance or industry - to have Director
command of all that is needed to conduct cutting edge work in psychiatric or
New insights still arise from data collected more than a decade ago. VIPBG
molecular geneticists and statisticians continue to analyze samples of DNA collect-
ed almost 20 years ago in a study of schizophrenia. Grants from NIH continue to
support analysis of data from large longitudinal studies of adult and juvenile twins
that began in the mid 80's and are only now reaching their completion.
Modern genetics poses new mathematical and computational challenges.
Institute faculty have obtained grants to develop new statistical approaches to
diagnosis and the daunting task of finding genes that affect behavior buried in the
haystack of the human genome.
Old data continue to inspire new studies. A study of the children of twins
Kenneth S. Kendler involves more than 2,000 families. A new study of the roles of genetic and envi-
Director ronmental influences in infant twins is just beginning in collaboration with the
University of Puerto Rico. International collaboration continues with scholars in
the U.S., The Netherlands, Norway, Sweden, United Kingdom and Australia. Some
of us are collaborating in twin studies of brain structure and function, others in studies of gene expression,
still others in aging. We are obtaining DNA samples in preparation for a large scale molecular-genetic study
of the interaction between genetic and environmental influences in risk to psychiatric and substance use dis-
orders. New methods of classifying and measuring liability to psychiatric and substance abuse disorders are
The future of Psychiatric Genetics requires new minds to grasp opportunities that are scarcely imag-
inable today. Recruitment of more pre- and post-doctoral students has led to
remodeling of space to accommodate them. We are proud that our NIMH pre-
and post-doctoral training grant was renewed at a time when funds were hard to
obtain. In addition to teaching formal graduate courses at VCU, VIPBG faculty
contribute to a series of international workshops in statistical genetics that have
graduated more than 1000 alumni over the last 15 years. This spring, many of us
worked on a text published by the APPI that tries to bring the principles of
Psychiatric Genetics to a wider audience of students and clinicians.
Forty years ago, the burning question was simply "Do genes affect behav-
ior?" Today's questions are more complicated and include: "Which genes affect
behavior?" "How do genetics and environmental risk factors inter-relate?" and Michael C. Neale
"How do genes act over time and through development to alter the chances of ill- Associate Director
ness." Tomorrow's questions will be yet more complex. We are planning to be
there to help answer them.
About Virginia Commonwealth University
Virginia Commonwealth University is an urban, public institution enrolling more than
28,500 undergraduate, graduate and first professional students on two campuses in Richmond,
Virginia. The Monroe Park Campus is situated in the heart of Richmond’s Fan District, a large
residential neighborhood of Victorian townhouses. The MCV Campus, which houses VCU’s
prestigious health sciences programs and the VCU Medical Center, is located two miles east of
the Monroe Park Campus in historic Court End, near the city’s government and financial cen-
More than 1,650 full-time faculty and 950 adjunct faculty comprise the university’s
teaching force. The total workforce of the university — faculty, physicians, nurses, and admin-
istrative and support staff — is more than 15,000. VCU attracts more than $140 million in spon-
sored research funding, placing it among
the top research institutions in the country.
Research strengths at VCU include
the basic and health sciences, business,
behavioral sciences, public affairs, and
the humanities. Among VCU’s many
national rankings are 20 graduate pro-
grams in the top tier of the U.S. News and
World Report review. For more informa-
The biomedical research strengths
of VCU have played a lead role in launch-
ing the Virginia Biotechnology Research
Park, a public-private partnership of the
university, surrounding localities, the state and the business community. VCU is comprised of
the schools of Allied Health Professions, the Arts, Business, Dentistry, Education, Engineering,
Medicine, Nursing, Pharmacy and Social Work, and the College of Humanities and Sciences,
which includes the L. Douglas Wilder school of Government and Public Affairs and the schools
of Mass Communications and World Studies. The academic units offer the following degree pro-
grams: 54 baccalaureate, 62 master’s, 24 doctoral, and first professional degrees in dentistry,
medicine and pharmacy.
The governance system of the university is headed by the Board of Visitors, a 16-member
body appointed by the governor of Virginia. This group has the legal authority and responsibil-
ity for Virginia Commonwealth University as established by legislation passed by the General
Assembly of Virginia. The president is selected by and responsible to the Board of Visitors,
which determines major policies for the university.
The University Council, made up of 75 members including faculty, students, administra-
tors and four subcommittees — the Executive Committee, the Committee on Student Affairs, the
Committee on Academic Affairs and the Committee on Faculty Affairs — meets monthly
September to May to review proposals for new policies and programs, as well as changes in
existing policies and programs.
About the Institute
Created in 1996, VIPBG is directed jointly by Dr.
Lindon Eaves, Distinguished Professor of Human
Genetics, and Dr. Kenneth Kendler, Rachel
Brown Banks Distinguished Professor of
Psychiatry, who have collaborated for over 20
years. Faculty of VIPBG have their primary
appointments in either the Departments of
Psychiatry or Human Genetics. Researchers
within the Institute provide expertise and sup-
port to numerous VCU departments and pro-
grams (e.g. Psychology, Pharmacology, The
Massey Cancer Center) and have established col-
laborative arrangements with other universities,
federal agencies and industrial partners, (e.g.,
Institute of Psychiatry, London; Oxford
University; Harvard University; Duke University;
Glaxo Smith Kline). Many of these partnerships
are with renowned scholars in leading institu-
tions in the US and around the world.
The faculty at VIPBG have a longstanding record in training productive research scientists
in the areas of genetic epidemiology, and psychiatric and behavioral genetics. Two faculty
currently hold research career awards, both
funded through NIMH. A total of 15 faculty
hold 27 federally funded grants, most of them
through NIMH, NIDA, NIAAA and NINDS with
23 grants funded by other agencies.
VIPBG unites expertise in molecular genetics,
mathematical genetics, alcohol, nicotine and
other substance abuse disorders, genetics of
complex traits, psychiatry, clinical psychology,
epidemiology, data analysis, software develop-
ment and dissemination, establishment and
maintenance of large population-based twin
registries, ascertainment of large samples of
high-density families appropriate for linkage
analysis, and the study of minority populations.
Located in Virginia's Biotechnology Research Park adjacent to VCU's medical campus,
VIPBG occupies 16,200 square feet of customized contiguous office space on the first floor of
Biotech One. The space includes offices for faculty and staff, a state-of-the-art molecular genet-
ics laboratory, fire-resistant facilities for data storage, a conference room (capacity 15-20 peo-
ple) with a library, and a computer room. Faculty are supported by research assistants and
secretarial, fiscal, and computer staff, most of whom are supported from external grants.
Molecular Genetics Laboratory
Drs. Riley and Chen direct the Molecular Genetics Laboratory in the Department of
Psychiatry, which totals over 2800 square feet. It has 14 desk/lab bench stations and 45 linear
feet of bench space - the capacity for 16 lab staff. In addition to that, our lab has a dedicated com-
puter room, a dedicated bacterial/tissue culture room and a reagent preparation and storage
room. Equipment includes a stand-alone computer network, a Beckman Coulter SNPStream
12/48 multiplex SNP genotyping platform, a SpectruMedix 9610 96-capillary automated laser flu-
orescent sequencer, four Tetrad PCR machines, one LJL fluorescent plate reader (serving as both
FP-TDI SNP genotyping system and fluorimeter for DNA quantitation), one iCycler real time PCR
machine, one pyrosequencer and all small equipment necessary to our program of work
(hybridization ovens, centrifuges, hoods, incubators, shakers, etc.). Future equipment and plat-
form additions are planned. The lab currently has a dedicated computer room equipped with a
Novell server, which provides data transfer and back up services for all lab staff. Pentium-
equipped personal computers and two Unix servers are available for lab staff to plan and design
experiments, and to analyze data. For CPU-intensive data analysis and networking tasks, VIPBG's
computing facilities are available.
VIPBG computing resources comprise desktop and laptop PCs running Windows XP or
Linux, which are connected via switched ethernet to the local cluster of servers, to VCU research
computing, and to the Internet. The local cluster features 64-bit Unix systems, with up to 2Gb RAM
and 70Gb RAID disk space, and a Linux Beowulf cluster that incorporates a 250Gb RAID disk, 1Tb
Network Attached Storage and 15 AMD Opteron dual-processor nodes each with 2Gb RAM and
36Gb disk space. These high-speed workstations provide powerful CPU and networking performance
for computer-intensive applications common in genetic studies. FORTRAN and C compilers, SAS,
Splus, R, Mx, and various linkage & association software packages including Genehunter and Merlin
are installed. Most faculty and students access these machines with X-windows software running on
a local Pentium PC's. A separate linux server supplies standard word processing and office software
and provides PC backup and printing services via central HP and Xerox laser printers.
VCU's central research computing facilities include two SGI Origin 2000 multiprocessor sys-
tems, a 52-node Linux beowulf cluster, and a Sun 420R 4 processor system, and these are supported
by approximately 20 Gb RAM and two terabytes of disk storage.
In the Bioinformatics Lab, we are working interactively on the study of gene struc-
tures of schizophrenia susceptibility genes (e.g. DTNBP1), on the design and establish-
ment of a comprehensive bioinformatics system to efficiently manage various types of
data, and on the development of computational tools for lab experimental support (e.g.
PCR primer design, selection of candidate genes or genetic markers). For more informa-
tion, go to www.bioinfo.vipbg.vcu.edu
Versatile Software for Biomedical Genetic Applications
The Structural Equation Modeling Package Mx, created by Dr. Michael Neale, is a
comprehensive user-friendly resource with a powerful graphical user interface for the sta-
tistical analysis of genetically informative data that is being used worldwide.
Population-Based Twin Registries
VCU scientists spearheaded the creation of the Mid-Atlantic Twin Registry
(MATR) through merging of the Virginia, North Carolina and South Carolina Twin
Registries. The MATR is directed and maintained by VIPBG personnel and currently has
enrolled more than 51,000 individual twins, making it one of the largest population-
based resources for genetic research in the world. The MATR currently is providing
research participants for seven projects and later this year will expand its efforts to sup-
port recruitment for and operation of three additional projects. All MATR operations and
affiliated studies are governed by the MATR's suite of more than 80 standard operating
procedures, which ensures consistent approach to all research subjects and protection of
their rights and privacy.
High-Density Family Collections
Successful linkage studies in complex illnesses such as psychiatric and substance
use disorders require large samples of families with multiple affected members. VIPBG
houses the world's largest collection of high density schizophrenia families, and growing
samples of families with epilepsy, alcoholism, nicotine-dependence and attention-deficit
hyperactivity disorder (ADHD).
VIPBG Faculty and Staff
Faculty Jill Opalesky, M.S.
Xiangning “Sam” Chen, Ph.D. email@example.com
Assistant Professor of Human Genetics and
Psychiatry, Co-director of Molecular Genetics Lab Carol A. Prescott, Ph.D.
firstname.lastname@example.org Associate Professor of Psychiatry
Linda A. Corey, Ph.D.
Professor of Human Genetics Brien P. Riley, Ph.D.
email@example.com Assistant Professor of Human Genetics and
Psychiatry, Co-director of Molecular Genetics Lab
Lindon J. Eaves, Ph.D. firstname.lastname@example.org
Distinguished Professor of Human Genetics
and Professor of Psychiatry, Co-director Judy L. Silberg, Ph.D.
of VIPBG Associate Professor of Human Genetics
Debra L. Foley, Ph.D. Edwin van den Oord, Ph.D.
Assistant Professor of Human Genetics Associate Professor of Psychiatry
John M. (Jack) Hettema, M.D., Ph.D. Zhongming Zhao, Ph.D.
Assistant Professor of Psychiatry Assistant Professor of Psychiatry and the
email@example.com Center for the Study of Biological Complexity
Kristen C. Jacobson, Ph.D.
Assistant Professor of Psychiatry Research Associates
Steven Aggen, Ph.D.
Kenneth S. Kendler, Ph.D. Department of Psychiatry
Rachel Brown Banks Distinguished Professor of firstname.lastname@example.org
Psychiatry, Professor of Human Genetics, Co-
director of VIPBG Charles Gardner, Ph.D.
email@example.com Department of Psychiatry
Hermine H. Maes, Ph.D.
Assistant Professor of Human Genetics Po-Hsiu Kuo, Ph.D.
firstname.lastname@example.org Department of Psychiatry
Donna R. Miles, Ph.D.
Assistant Professor of Human Genetics John Myers, M.S.
email@example.com Department of Psychiatry
Michael C. Neale, Ph.D.
Professor of Psychiatry and Human Genetics Jaime Robles, Ph.D.
firstname.lastname@example.org Departments of Psychiatry and Human Genetics
Thomas Kubarych, Ph.D. Vladimir Vladimirov, M.D., Ph.D.
Department of Psychiatry Department of Psychiatry
Timothy York, Ph.D.
Postdoctoral Fellows Departments of Psychiatry and Human Genetics
Charles Anderson, Ph.D.
Department of Psychiatry Lan Zhang, M.D., Ph.D.
email@example.com Department of Psychiatry
Paul Andrews, Ph.D.
Department of Psychiatry Graduate Students
Jozsef Bukszar, Ph.D. Department of Psychology
Department of Psychiatry firstname.lastname@example.org
Nathan Gillespie, Ph.D. Department of Integrative Life Sciences
Department of Psychiatry email@example.com
James Eric Schmitt
Robin Page Goin-Kochel, Ph.D. Department of Human Genetics
Department of Psychiatry firstname.lastname@example.org
Cizhong Jiang, Ph.D. Department of Human Genetics
Dept. of Psychiatry email@example.com
Molecular Genetics Lab
Gursharan Kalsi, Ph.D.
Department of Psychiatry Seon-Sook An, Ph.D.
firstname.lastname@example.org Lab Specialist
Joseph McClay, Ph.D.
Departments of Psychiatry and Human Genetics Shaon Hossain
email@example.com Lab Specialist
Daekwan Seo, Ph.D.
Department of Psychiatry Robert Ribble
firstname.lastname@example.org Lab Specialist
Dawn Thiselton, Ph.D.
Department of Psychiatry Jennifer Vittum
email@example.com Lab Specialist
Cristina Vargas-Irwin, Ph.D.
Department of Psychiatry Xu Wang
firstname.lastname@example.org Lab Specialist
Brandon Wormley Karen Beebe
Lab Specialist Research Assistant
Psychiatry Staff Administrative Office Specialist
Fiscal Technician Terry Crosby
email@example.com Research Specialist
Frank Butera, M.A.
Research Specialist Eric Doersch
firstname.lastname@example.org Programmer/ Network Administrator
Financial Services Manager Melissa Hayes
email@example.com Adminstrative Office Specialist
Lisa Halberstadt, M.S.
Research Specialist Sandy Lee-Muzik
firstname.lastname@example.org Research Specialist
Barabara L.S. Herrmann
Admin Office Specialist Terry Martin, M.S.
email@example.com Research Specialist
Administrative Assistant Anne Taylor-Morris
firstname.lastname@example.org Research Specialist
Info Tech Specialist Gwen Reilly
email@example.com Research Specialist
Administrative Office Specialist Patricia Solari
firstname.lastname@example.org Research Assistant
Systems Analyst Elizabeth Thomas
email@example.com MATR Project Coordinator
Human Genetics Staff
Cindy Beck Info Tech Specialist
MATR Applications Analyst firstname.lastname@example.org
Susan Williams, M.S.
Major Areas of Research
VIPBG's multidisciplinary research is organized around two mutually reinforcing principal
themes: the development of methods for the analysis of genetic and environmental risk to
complex traits (statistical genetics and genetic epidemiology) and the gathering of empiri-
cal data that permit the analysis of the causes of medically relevant normal behavioral
variation and biomedical conditions with behavioral components (molecular, substance
abuse, psychiatric and behavioral genetics).
Currently, VIPBG is supported by research grants totaling over $25 million from federal
and private sources, including 25 R01's, two K awards and a T32 National Research
Scholarship Award. More than 500 papers in leading journals have been authored or co-
authored by VIPBG faculty. In a recent survey of high-impact research in psychiatry, VCU
was ranked second among federally funded U.S. universities (http://www.in-
cites.com/research/2005/march_21_2005-2.html). Three VIPBG researchers are ranked
among the top 20 highly cited in psychiatry worldwide.
Listed here are the major areas of research that make up VIPBG’s core responsibilities.
More specific grant descriptions can be found beginning on page 19.
VIPBG is currently working on a number of projects concerning schizophrenia. One of the major
projects is funded by the National Institutes of Mental Health. Principal Investigators are Drs.
Kenneth Kendler and Brien Riley. The study focuses on the characterization and understanding of
the dysbindin gene, the first widely replicated susceptibility gene for schizophrenia, found in our
laboratory three years ago.
A second major project in schizophrenia, funded by the National Institute for Research on
Schizophrenia and Depression (NARSAD), is being conducted by Dr. Xiangning Chen. His team is
working to characterize and find the susceptibility locus for schizophrenia under the 5q linkage
One of the major projects at VIPBG concerning nicotine dependence is titled “Genetic Etiology of
Tobacco Initiation and Nicotine Dependence” and is funded by the Tobacco Settlement
Foundation from the Commonwealth of Virginia. It is being conducted in collaboration with Drs.
Xiangning Chen and Kenneth Kendler. A strategy is being used for testing candidate genes using a
modified case control sample to be able to test specifically for genes predisposing to initiation and
genes predisposing to nicotine dependence conditional upon initiation.
Dr. Judy Silberg conducts two of VIPBG’s studies on depression. She received a NARSAD award for
studying the influence of genetic (in particular the serotonin transporter gene, 5HT) and environmen-
tal factors in the development of young adult depression. The title of the project is “Genetic and envi-
ronmental pathways to young adult depression.” Dr. Silberg also heads the NIMH funded study,
"Parental effects on depression and disruptive behavior in children of twins.”
Dr. Kenneth Kendler is currently conducting additional research and collaboration with Nancy
Pedersen of the Karolinska Institute examining depression in the largest interview-based twin sample
yet studied of over ten thousand twin-pairs. They are examining gender differences, age of onset
effects, and the inter-relationship between risk for depression and risk for cardiovascular disease.
Substance Use and Abuse/Dependence
The “Irish Affected Sib Pair Study of Alcohol Dependence” study, led by Dr. Carol Prescott, is a major
project of VIPBG’s, where the goals are to study the genetic epidemiology of alcoholism and alcohol-
related behaviors, susceptibility genes for alcohol dependence, and the genetic basis of individual dif-
ferences in personality and cognition. To conduct this project, a team of experts has been assembled
in clinical assessment, statistical genetics and molecular genetics.
Dr. Kenneth Kendler is involved in the analyses of existing data from a comprehensive program of
research looking at the genetics of substance use and abuse/dependence. In development since 1983,
this research program is supported by a number of major twin studies.
Dr. Michael Neale’s recently funded project, “Psychometric and genetic assessments of substance
use,” develops, tests, and applies methods to investigate the assessment and classification of sub-
stance use and abuse patterns, including genetic item response theory models and genetic latent class
models. Collaborators on this project include Drs. Dorret Boomsma and Jacqueline Vink at Free
University of Amsterdam, Dr. Brian Flaherty at University of Washington, Seattle, and Dr. Gitta
Lubke at University of Notre Dame.
Development of Analytic Techniques
Dr. Edwin van den Oord and his group of researchers have focused on the study and development of
techniques for the analysis of large scale genetic data with an application to psychiatric and behav-
ioral phenotypes. Examples of specific areas are data mining and knowledge discovery, control of
false discoveries, phenotype refinement and psychometrics, and the statistical modeling of the inter-
play of genes and environment. Specific applications include schizophrenia, depression, and respira-
Assessment of Psychopathology
The project, “Psychopathology: Models, Measurement, and Classification,” headed by Dr. Michael
Neale, develops and applies an array of methods to examine the empirical basis for the DSM noso-
logical system and will develop more efficient methods of analysis of the available data. Existing
methods applied to these data include latent class analysis, item response theory, multiple rater
models and modern regression methods. Extensions of these methods have been developed and
applied, particularly multiple rater models for longitudinal data, multivariate contingent causal
models for ordinal data, and structured versions of latent class and item response models that are
suitable for the analysis of data collected from families or other clustered groups. The long term
goals of the project are to improve the efficiency of measurement, nosology, and knowledge of the
etiology of common psychiatric disorders and their comorbidity.
Child and Adolescent Development
A number of studies headed by Drs. Lindon Eaves and Judy Silberg look at the development of
children and adolescents. In one of their studies, the analysis of the interplay of genes and envi-
ronment and ageing is conducted.
The “Children of Twins” study, just recently initiated, unravels the causal effects of parent treat-
ment on offspring behavior from secondary genetic association between parents and children.
Drs. Silberg and Eaves hope to find out whether the genes or environment influence the associa-
tion between aspects of the home environment such as marital conflict, maternal smoking in
pregnancy or parents psychopathology and children disorders such as depression and anti-social
“Research Training: Psychiatric and Statistical Genetics” is a program headed by Dr. Michael Neale to
support multi-disciplinary training in Psychiatric and Behavioral Genetics. Training usually consists of
4-5 years in duration for predoctoral and 2-3 years for postdoctoral students. Applicants are accepted
from a broad array of disciplines, including medicine, psychiatry, psychology, biostatistics, neuro-
science, molecular genetics and biology.
Drs. Hermine Maes, Lindon Eaves, and Timothy York are co-investigators on the research training pro-
gram, “Pre- & Post-doctoral Training Program in Cancer Control.” The overarching aim of this program
is to provide high quality training in cancer control and generate a group of young scientists with
unique research skills. Training occurs in the Massey Cancer Center and Virginia Commonwealth
University including research in quality care/health services, cancer prevention interventions and dis-
parity issues, genetic influences using large twin and family databases, and cancer-related pain and
quality of life.
A number of great accomplishments we are proud to announce have occurred in the past
year at VIPBG. Below is a list of some of those. If you are interested in acquiring more
information on any of the following, please contact the researcher named at the end of each.
1. The project, "Axis I and Axis II Psychiatry Disorders in Norwegian Twins" has been fund-
ed by NIMH. This is a collaborative project with colleagues in Norway to conduct both pre-
liminary and extensive analyses of the first interview-based assessed sample of twins for a
complete set of Axis I and Axis II psychiatric disorders. (Dr. Kenneth Kendler)
2. The National Institute for Child Health and Development (NICH) ia awarding VIPBG
$1.5M for a study of infant twins in Puerto Rico. The title of the grant is "Gene environment
interplay in infant development” and represents a collaborative effort between VCU (Drs.
Eaves and Silberg), Drs. Glorisa Canino and Vivian Febo at the University of Puerto Rico,
and Dr. Helen Egger, a child psychiatrist at Duke University. The collaboration between
UPR and VCU was originally established by VCU's president, Eugene Trani in 1999. (Dr.
3. VIPBG has received the four year renewal of the NIDA grant entitled "Twin Family Study
of Drug Use, Abuse and Dependence." This project is funded for three years of extensive
data analysis on this retrospective developmental study of detailed genetic and environmen-
tal risk factors for substance use, abuse and dependence. (Dr. Kenneth Kendler)
1. Association signals have been observed with schizophrenia in two candidate genes, AKT1
and TRAR4. (Drs. Dawn Thiselton, Vladimir Vladimirov, and Brien Riley)
2. An additional area of research at VIPBG, currently unfunded, is in the philosophical and
conceptual issues within psychiatry in general and psychiatric genetics more specifically.
Dr. Kenneth Kendler has been writing a series of review papers trying to summarize and
articulate the deeper conceptual issues in the field. (Dr. Kenneth Kendler)
3. A new cross-platform application was created called Iga972 for optimizing two-stage
linkage disequalibrium studies. (Drs. Jaime Robles and Edwin van den Oord)
4. Three small affective neuroscience pilots are in the works: One is being conducted with
Dr. Scott Vrana looking at modulation of acoustic startle, as well as, response of facial
musculature, pulse, and galvanic skin response to a series of affectively charges slides.
The second project is being conducted in collaboration with Dr. Danny Pine and involves
higher-tech computer-based assessments of a variety of affectively related constructs.
The third is a project being conducted in collaboration with Dr. Paul Ekman which
involves the analysis of facial response, emotional stimuli in separated identical and fra-
ternal twin-pairs collected through the famous Minnesota Twin-Registry. (Dr. Kenneth
5. A genome scan of 511 sibling pairs to identify susceptibility genes for alcohol depend-
ence has been completed. (Dr. Carol Prescott)
6. Multivariate analyses have identified shared genetic risk between major depression, a
range of anxiety disorders, and trait neuroticism. (Dr. Jack Hettema)
7. Publication in the American Journal of Psychiatry, a review article entitled "Toward a
Philosophical Foundation of Psychiatry." This is the first comprehensive philosophical
analysis of critical conceptual issues in the field of psychiatry published in a major psy-
chiatric journal in the last decade. (Dr. Kenneth Kendler)
8. Analyses of symptoms of depression indicate that while assessment is good for those at
high risk, it is poor for most of the general population. (Dr. Steven Aggen)
VIPBG Publications from July 2004 to June 2005
Aggen SH, Neale MC, Kendler KS. (2005) DSM Chen X, Dunham C, Kendler S, Wang X, O'Neill
criteria for major depression: evaluating symptom FA, Walsh D, Kendler KS. (2004) Regulator of G-
patterns using latent-trait item response models. protein signaling 4 (RGS4) gene is associated with
Psychol Med 35(4):475-87 schizophrenia in Irish high density families. Am J
Med Genet B Neuropsychiatr Genet 129(1):23-6.
Agrawal A, Neale MC, Jacobson KC, Prescott
CA, Kendler KS. (2005) Illicit drug use and Coventry WL, Gillespie NA, Heath AC, Martin NG.
abuse/dependence: modeling of two-stage variables (2004) Perceived social support in a large communi-
using the CCC approach. Addict Behav 30(5): 1043- ty sample--age and sex differences. Soc Psychiatry
8. Psychiatr Epidemiol 39(8):625-36.
Agrawal A, Neale MC, Prescott CA, Kendler Crider A, Kremen WS, Xian H, Jacobson KC,
KS. (2004) A twin study of early cannabis use and Waterman B, Eisen SA, Tsuang MT, Lyons MJ.
subsequent use and abuse/dependence of other illic- (2004) Stability, consistency, and heritability of
it drugs. Psychol Med 34(7): 1227-37. electrodermal response lability in middle-aged male
twins. Psychophysiology 41(4):501-9.
Agrawal A, Prescott CA, Kendler KS. (2004)
Forms of cannabis and cocaine: a twin study. Am J Dawood, K., Kirk, K. M., Bailey, J. M., Andrews, P.
Med Genet B Neuropsychiatr Genet 129(1):125-8. W., & Martin, N. G. (2005) Genetic and environ-
mental influences on the frequency of orgasm
Bartels M, van den Oord EJ, Hudziak JJ, Rietveld in women. Twin Research and Human Genetics 8:
MJ, van Beijsterveldt CE, Boomsma DI. (2004) 27-33.
Genetic and environmental mechanisms underlying
stability and change in problem behaviors at ages 3, Eaves L, Silberg J, Foley D, Bulik C, Maes H,
7, 10, and 12. Dev Psychol 40(5):852-67. Erkanli A, Angold A, Costello EJ, Worthman C
(2004) Genetic and environmental influences on the
Breslau J, Kendler KS, Su M, Gaxiola-Aguilar S, relative timing of pubertal change. Twin Research
Kessler RC. (2005) Lifetime risk and persistence of 7:471-81
psychiatric disorders across ethnic groups in the
United States. Psychol Med 35(3):317-27. Eaves LJ, Silberg JL. (2005) Parent-child feed-
back predicts sibling contrast: using twin studies to
Caspi A, Moffitt TE, Cannon M, McClay J, Murray test theories of parent-offspring interaction in infant
R, Harrington H, Taylor A, Arseneault L, Williams behavior. Twin Res Hum Genet 8(1):1-4.
B, Braithwaite A, Poulton R, Craig IW. (2005)
Moderation of the effect of adolescent-onset Fanous AH, Kendler KS. (2005) Genetic hetero-
cannabis use on adult psychosis by a functional geneity, modifier genes, and quantitative pheno-
polymorphism in the catechol-O-methyltransferase types in psychiatric illness: searching for a frame-
gene: longitudinal evidence of a gene X environment work. Mol Psychiatry 10(1):6-13.
interaction. Biol Psychiatry 57(10):1117-27.
Foley DL, Rutter M, Angold A, Pickles A, Maes
Chen X, Wang X, O'Neill AF, Walsh D, Kendler HM, Silberg JL, Eaves LJ. (2005) Making sense
KS. (2004) Variants in the catechol-o-methyltrans- of informant disagreement for overanxious disorder.
ferase (COMT) gene are associated with schizophre- J Anxiety Disord 19(2):193-210.
nia in Irish high-density families. Mol Psychiatry
9(10):962-7. Foley DL, Pickles A, Maes HM, Silberg JL,
Eaves LJ. (2004) Course and short-term outcomes
Chen X, Wu B, Kendler KS. (2004) Association of separation anxiety disorder in a community sam-
study of the Epac gene and tobacco smoking and ple of twins. J Am Acad Child Adolesc Psychiatry
nicotine dependence. Am J Med Genet B 43(9):1107-14.
Neuropsychiatr Genet 129(1):116-9.
Foley DL, Eaves LJ, Wormley B, Silberg JL, Kendler KS, Gardner CO, Jacobson KC,
Maes HH, Kuhn J, Riley B. (2004) Childhood Neale MC, Prescott CA (2005) Genetic and envi-
adversity, monoamine oxidase a genotype, and risk ronmental influences in illicit drug use and tobacco
for conduct disorder. Arch Gen Psychiatry use across birth cohorts. Psychological Medicine
Geithner CA, Thomis MA, Vanden Eynde B, Maes Kendler KS, Myers J, Prescott CA. (2005) Sex
HH, Loos RJ, Peeters M, Claessens AL, Vlietinck R, differences in the relationship between social sup-
Malina RM, Beunen GP. (2004) Growth in peak aer- port and risk for major depression: a longitudinal
obic power during adolescence. Med Sci Sports study of opposite-sex twin pairs. Am J Psychiatry
Exerc 36(9):1616-24. 162(2):250-6.
Gillespie NA, Whitfield JB, Williams B, Heath AC, Kendler KS. (2005) Psychiatric genetics: a
Martin NG. (2005) The relationship between stress- methodologic critique. Am J Psychiatry 162(1):3-11.
ful life events, the serotonin transporter (5-HTTL-
PR) genotype and major depression. Psychol Med Kendler KS, Kuhn JW, Prescott CA. (2004)
35(1):101-11. Childhood sexual abuse, stressful life events and risk
for major depression in women. Psychol Med
Gillespie NA, Evans DE, Wright MM, Martin NG. 34(8):1475-82.
(2004) Genetic simplex modeling of Eysenck's
dimensions of personality in a sample of young
Australian twins. Twin Res 7(6):637-48.
Hettema JM, Prescott CA, Myers JM, Neale
MC, Kendler KS. (2005) The structure of genetic
and environmental risk factors for anxiety disorders
in men and women. Arch Gen Psychiatry
Goin-Kochel, R.P. & Myers, B.J. (2005) Parental
report of early autistic symptoms: Differences in
ages of detection and frequencies of characteristics
among three autism-spectrum disorders. Journal on
Developmental Disabilities 11(2): 21-39.
Haller DL, Miles DR, & Cropsey KL. (2004) Kendler KS, Aggen SH, Prescott CA,
Smoking stage of change is associated with retention Jacobson KC, Neale MC. (2004) Level of family
in a smoke-free residential drug treatment program dysfunction and genetic influences on smoking in
for women. Addictive Behaviors 29: 1265-1270. women. Psychol Med 34(7):1263-9.
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Kerns RT, Ravindranathan A, Hassan S, Cage MP,
Kendler KS, Kuhn JW, Vittum J, Prescott York T, Sikela JM, Miles MF. (2005) Ethanol
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Kjeldsen MJ, Corey LA, Solaas MH, Friis ML, Mowry BJ, Holmans PA, Pulver AE, Gejman PV,
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Kubarych, TS, Aggen, SH, Hettema, JM, Nakken KO, Solaas MH, Kjeldsen MJ, Friis ML,
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Active Research Grants
1. AD Williams 5. Bank of America
Candidate Genes in Anxiety Disorders Parental Effects on Childhood Behavior in
PI: Jack Hettema the Offspring of Twins (Hazel Thorpe Carmen
The main purpose of this grant is to collect pilot and George Gay Carmen Trust Research)
data for case-control genetic association analyses of PI: Judy Silberg
candidate genes for anxiety disorders using patients This is a five-year study to analyze the non-genetic
from the VCU psychiatry clinic. contributions of family background to risk to child-
hood and adolescent depression and conduct dis-
2. AD Williams turbance. The unique power of the design lies in the
Candidate Gene Studies of Anorexia Nervosa use of 2320 adult MZ and DZ twins with their
PI: Brien Riley spouses and children ascertained from approxi-
This project aims to initiate a pilot study of four mately 100,000 adults twins that will be ascer-
genes with plausible biological hypotheses and posi- tained through the Mid-Atlantic Twin Registry.
tional evidence from linkage studies for involvement
in AN. This project will bring together the expertise 6. GlaxoSmithKline
of two researchers who have not previously collabo- The Genetic Epidemiology of Psychiatric
rated to develop VCU's first study of the molecular and Respiratory Phenotypes
genetics of eating disorders. PI: Edwin van den Oord
The aim of this project is to analyze complex large
3. AD Williams scale genetic epidemiological data with novel statis-
Behavioral and Genetic Markers of Drug tical methods to produce new phenotype and genet-
Addiction in an Adolescent Murine Model ic understanding of psychiatric and respiratory
PI: Edwin van den Oord phenotypes.
The progression towards addictive behavior has
been described as involving the transition through 7. MCC
several stages, beginning with the initial contact Identification of biomarkers for tobacco
with the drug, followed by its regular use, which, in use: Normal variation and the control of
turn, may finally result in substance dependence, or gene expression in MZ and DZ twins
addiction. This project’s aim is to develop new high- PI: Tim York
throughput phenotype measures of the addiction This project is designed to characterize genetic and
proves plus risk factors such as impulsivity and like environmental sources of individual variation in
those to genetic variation. gene expression profiles and evaluate the role of
gene expression in mediating the impact of known
4. AD Williams risk factors for cancer, tobacco use, alcohol use, and
Neighboring-Nucleotide Effects on Single obesity.
Nucleotide Polymorphisms in the Mouse
Genome 8. NARSAD
PI: Zhongming Zhao Exploring the use of haplotype maps to
In this project, the aim is to perform an initial detect susceptibility to schizophrenia
analysis of the sequence context of SNPs in the PI: Edwin van den Oord
mouse genome, to compare that to what is found in In this pilot study, the aim consists of a small hap-
the human genome, and to further establish an effi- lotype map-based search to detect susceptibility
cient system for the emerging data. It will be the genes for schizophrenia.
first investigation of the SNP neighboring sequence
context in the mouse genome.
9. NARSAD 13. NARSAD
Using Biological haplotypes to identify A Bioinformatics Approach to Studying
susceptible genes for schizophrenia Schizophrenia Susceptibility Genes
PI: Xiangning Chen PI: Zhongming Zhao
In this project, the aim is in a new approach to iden- In this project, the aim is in a bioinformatics
tify susceptible haplotypes for schizophrenia for the approach to first investigate the structures of candi-
5q22-31 linkage peak implicated in the genome scan date genes for schizophrenia and reveal the evolu-
study of the Irish high density schizophrenia fami- tionary and functional changes.
lies. The plan is to establish chromosome 5 specific
hybrid haploid cell lines for a few families of the 14. NARSAD
Irish subjects who were linked to the chromosome African Haplotype Studies of Schizophrenia
linkage peak. Genotyping these individual chromo- Candidate Genes
somes would enable us to obtain biological haplo- PI: Brien Riley
types for these subjects. This project’s goal is to genotype sufficient single
genetic markers in samples of 23 South African
10. NARSAD Bantu multiply-affected families (44 cases, N=129)
Understanding Influences on Comorbidity and 113 Ethiopian Gurage cases plus parents and
between ASB and MDD population controls (N=300) to identify haplotype
PI: Kristen Jacobson block structure and assess evidence for association
The main purpose of this project is to provide two of these genes with schizophrenia. We will follow up
years of salary support for Dr. Jacobson during her positive evidence with sequencing to identify liabili-
first few years as an Assistant Professor at the ty alleles or further genotyping as appropriate.
Virginia Institute for Psychiatric and Behavioral
Genetics in the Department of Psychiatry at the 15. NARSAD
Medical College of Virginia of Virginia Investigation into a Candidate Susceptibility
Commonwealth University (MCV/VCU). The objec- Locus for Schizophrenia on Xp11.23: a
tive of this funding is use a genetically informative Microdeletion Segregating with X-linked
design to examine the relationship between depres- Retinitis Pigmentosa in a Small Family
sive symptoms and antisocial behavior. PI: Dawn Thiselton
This project investigates the potential role of genes
11. NARSAD in schizophrenia, by 1) assessing a larger sample of
Genetic Heterogeneity of Major Depression: familial cases and control individuals for deletions
A Twin Study of Comorbidity overlapping this interval by STS screening of affect-
PI: Carol Prescott ed males 2) conducting association analyses
This project’s purpose is to fund the analysis of data between polymorphic variants in the deleted genes
from the Virginia Adult Twin Study of Psychiatric (other than RP2) and disease 3) fully characterizing
and Substance Use Disorders (VATSPSUD), a longi- the deleted genes as to genomic organization and
tudinal study of more than 9000 twins and their transcriptional expression, to pave the way for
parents. The goal of this project is to clarify the future studies into their function in the healthy and
mechanisms underlying the comorbidity between schizophrenic brain.
major depression (MD) and substance use disorders
(SUD), including alcoholism, nicotine dependence, 16. NCI 93423 R25
and abuse of illicit substances (cannabis, cocaine, Pre- & Post-doctoral Training Program in
stimulants, sedatives, opiates, and hallucinogens). Cancer Control
Co-PI: Hermine Maes
12. NARSAD The overarching aim of this grant is to provide high
Genetic and environmental pathways to quality training in cancer control and generate a
young adult depression group of young scientists with unique research
PI: Judy Silberg skills. We provide pre-doctoral training in the areas
This grant is a study of young adult depression with of human genetics, biostatistics and psychology and
a focus on the interaction of the 5HT (the serotonin pre- and post-doctoral training in a multidiscipli-
transporter gene) with life events in predicting nary environment in behavioral science, behavioral
depressive disorders in young adults. genetics and genetic epidemiology, health services
research and palliative care.
17. NIA 18384 R01 21. NIDA 14041 K12
A Longitudinal Twin Study of Cognition and Building Research Careers in Women's
PI subc: Lindon Eaves Scholars: Donna Miles, Kristen Jacobson
The goal of this project is to conduct a longitudinal To increase the number of researchers, Virginia
study to investigate ways in which genes and envi- Commonwealth University (VCU) has established an
ronmental factors contribute to cognitive and adap- Interdisciplinary Women's Health Research (IWHR)
tive aging, and how the relative influence of genes scholars program. The program will be based on a
and environmental factors may change over time. strong research foundation in five areas relevant to
We study the now middle-aged subjects from the women's health: substance abuse, psychiatric genet-
Vietnam Era Twin Registry who we have been ics, reproductive health, cancer, and diseases associ-
studying for the past 12 years. ated with aging.
18. NIAAA 11408 R01 22. NIDA 018673 R01
Irish Affected Sib Pair Study of Alcohol Psychometric and Genetic Assessments of
Dependence Substance Use
PI: Carol Prescott PI: Michael Neale
The goal of this project is to detect the genomic This project aims to develop a series of novel
location of susceptibility loci (SL) for alcoholism. approaches to phenotyping drug use and abuse. The
Identifying the location of these genes is the first general scheme is to develop statistical models from
step toward understanding their mechanism of theory, implement them in user friendly software,
action and developing more effective treatments. To and examine their statistical properties.
conduct this project, we have assembled a team of
experts in clinical assessment, statistical genetics 23. NIMH 41953 R01
and molecular genetics. The Genetic Epidemiology of Schizophrenia
19. NICHD 1R01HD049685-01 PI: Kenneth Kendler
Gene environment interplay in infant In this third and final submission of this competitive
development renewal, the goal is to critically extend the Irish
PI: Judy Silberg Study of High-Density Schizohprenia Families
This study’s aim is to extend the collaborative (ISHDSF) by collecting 500 proband-parent triads
Puerto Rican Infant Twin Study ("PRINTS") for for family-based association studies. We have select-
characterizing the interplay of genes and the family ed triads with a positive family history of psychosis
environment in the development of behavioral prob- to reduce the rate of "phenocopies,” interview par-
lems and psychopathology in preschool children. ents for their personal and family history of schizo-
phrenia and schizophrenia spectrum illness so as to
20. NIDA 011287 R01 weight transmissions on the basis of the probability
A Twin-Family Study of Drug Use, Abuse, that they contain a susceptibility allele and sample
and Dependence all living and available relatives with schizophrenia
PI: Kenneth Kendler or chronic schizoaffective disorder so as to weight,
This competitive renewal is for 4 years of support in those triad-families, those that are more likely to
for a series of detailed analyses of a unique twin be segregating a susceptibility allele in a given chro-
data set, collection of which is now nearing comple- mosomal region.
tion. We articulate 4 primary aims: 1. The
Development of PSUD. 2. Contextual Factors 3. 24. NIMH 45712 R01
Heterogeneity 4. Sequella - Given an initial episode Familial Psychiatric Disorder & Attention in
of PSU, we will explore what predicts further use Schizophrenia
and the development of PSUD. Given the develop- PI subc: Kenneth Kendler
ment of PSUD, we will clarify the factors that pre- This project’s goal is to replicate and extend impor-
dict subsequent adult outcomes. tant findings from the first phase of this project
indicating that there is a significantly increased
familial aggregation of schizophrenia, schizophrenia
spectrum personality disorders, and certain neu-
rocognitive impairments in families of probands
with childhood-onset schizophrenia compared to
families of community control and adult-onset
25. NIMH 49492 R01
30. NIMH 65320 R01
The Epidemiology of Mood, Anxiety and
Candidate Genes in Models of Adolescent
PI: Kenneth Kendler
PI: Edwin van den Oord
This project is a competitive renewal of a large-
The overall aim of this project is to facilitate the
scale, population based, longitudinal study of
integration of measured genotypes in etiological
female-female, male-male and male-female twin
models of behavioral traits and psychiatric disor-
pairs ascertained through the birth-certificate-based
Virginia Twin Registry. This grant supports further
data analysis focused on understanding sex differ-
31. NIMH 65322 R01
ences in risk for mood disorders.
Psychopathology: Models, Measurement and
26. NIMH 49716 R01
PI: Michael Neale
The Transmission of Vulnerability Factors
This project’s aim is to develop and apply an array
of methods to examine the empirical basis for the
PI subc: Kenneth Kendler
DSM nosological system and will develop more effi-
This project is designed to test key hypotheses
cient methods of analysis of the available data.
regarding the transmission of measurable nonsymp-
tomatic characteristics of individuals that reflect
32. NIMH 66277 K08
their predisposition to schizophrenia.
Genetics of Fear and Anxiety Disorders
PI: Jack Hettema
27. NIMH 60324 R01
This K08 Mentored Clinical Scientist Development
The Genetic Epidemiology of Juvenile
Award provides advanced research training in the
genetics of fear and anxiety disorders for Dr. John
PI: Debra Foley
M. Hettema, M.D., Ph.D. Specific research objec-
The goal of this project is to analyze longitudinal
tives examine self-report measures in anxiety disor-
data already collected at personal interview with a
ders, their relationship with personality traits like
large population-based sample of juvenile twins and
neuroticism, factors underlying comorbidity
their parents to develop a detailed understanding of
amongst the anxiety disorders and with depressive
the developmental genetic epidemiology of the more
disorders, and the relationship between experimen-
common juvenile anxiety disorders (separation anxi-
tal measures such as fear conditioning and self-
ety, overanxious disorder, phobias).
report fears. Dr. Hettema will also pilot an MRI
study in identical twin pairs concordant and discor-
28. NIMH 068881 R01
dant for anxiety disorders.
Multicenter Genetic Studies of
33. NIMH 068484 K01
PI: Brien Riley
Genetics of Vulnerability to Antisocial
This is a revised four-year competing project for col-
laborative linkage and association studies of schizo-
PI: Kristen Jacobson
phrenia in a multicenter sample of 860 informative
This project is to fund Kristen Jacobson to gain
pedigrees under a narrow diagnostic model.
training and experience in the measurement and
analysis of neuropsychological traits that may be
29. NIMH 62368 R01
related to vulnerability to antisocial behavior. The
Parental Effects on Depression and
candidate then applies this knowledge and experi-
Disruptive Behavior in Children of Twins
ence to the pilot data collection of neuropsychologi-
PI: Judy Silberg
cal traits and antisocial behavior from a sample of
This is a study proposed to analyze the non-genetic
25 adult, male-male sibling pairs, under the guid-
contributions of family background to risk to child-
ance of Scott Vrana, Ph.D., a co-sponsor of the
hood and adolescent depression and conduct distur-
application at Virginia Commonwealth University.
34. NIMH 068521 R01 39. VTSF 8520012
Developmental Genetic Epidemiology of Virginia Youth Tobacco Project:
Psychopathology Longitudinal Twin Study: Transitions to
PI: Lindon Eaves Substance Abuse
This five-year data analysis project is to yield a com- Co-PI: Donna Miles
prehensive understanding of the developmental A component of the Virginia Commonwealth Youth
interplay between genetic and social factors in the Tobacco Project, the purpose of this study is to
trajectory of mood and behavioral disorders from address basic etiological questions regarding the
early adolescence into young adulthood. transition from tobacco use to nicotine dependence
and to examine the role of genetic and environmen-
35. NIMH 068643 R01 tal factors that contribute to the progression of
Axis I & Axis II Psychiatric Disorders in tobacco use into nicotine dependence between ado-
Norwegian Twins lescence and young adulthood.
PI: Kenneth Kendler
The goal of this study is to conduct detailed analysis 40. VTSF 8520012
of a population-based study of young adult twins in Virginia Youth Tobacco Project: Candidate
Norway assessed using personal interviews for the Genes for Nicotine Dependence in Humans
lifetime history of both major axis I psychiatric and PI: Kenneth S. Kendler, Sam Chen
substance use disorders and all axis II disorders. The aim of the study is to identify and characterize
the individual genes that determine vulnerability to
36. Pfizer nicotine dependence (ND) in humans. Discovery of
Gender Differences in the Development of the specific genetic variants in humans which influ-
MDD and Anxiety Disorders ence liability to ND has important implications for
PI: Jack Hettema the reduction of the disease burden imposed by
The present study proposes to examine the risk fac- tobacco use.
tors for major depression and anxiety disorders and
attempt to understand what predicts their high 41. VTSF
comorbidity and increased prevalence in women. Genetic Etiology of Tobacco Initiation and
Multivariate regression, discrete-time survival Nicotine Dependence
analysis, and structural equation modeling will be PI: Kenneth Kendler
utilized to understand the multistage process of the This project aims to clarify the role of genetic, family
development of comorbidity between depression environmental, and individual-specific environmen-
and anxiety. tal risk factors in the etiology of tobacco initiation
and the progression to nicotine dependence. We aim
37. Thomas F. and Kate Miller Jeffress Memorial Trust to use molecular tools to identify individual genes
Analysis of Genetic Variation in Human CpG that influence vulnerability to tobacco initiation and
Islands the progression to nicotine dependence.
PI: Zhongming Zhao
This study aims to investigate the distribution and
patterns of single nucleotide polymorphisms in CpG
islands or in promoter-associated CpG islands in the
Linkage Disequilibrium Mapping of
Susceptibility Genes for Schizophrenia
PI: Brien Riley
One of the goals of this study is to genotype
microsatellite markers in the Irish Study of High
Density Schizophrenia Families (ISHDSF) more
densely in the region corresponding to the 95% con-
fidence interval (CI) for linkage on chromosome
Research Initiatives for 2005-6
1. Initiation of the Clinical Outcome Study of Autism Genetics
This study has been in the planning stages for several years. With key collaborators
at several other centers and institutions, as well as some potential funding from a
private foundation, we plan to begin site and sample recruitment during 2005-
2006. (Dr. Brien Riley)
2. Candidate-gene genetic association studies
Using multivariate anxiety-depression phenotype with subjects selected for very
high or very low genetic loading. (Dr. Jack Hettema)
3. Brain Imaging
Brain imaging of twins concordant or dis-
cordant for anxiety disorders. (Dr. Jack
4. SIBS4 project
The "SIBS4" project in collaboration with
Drs. Mike Neale, Leena Peltonin and
Jouko Lonnqvist. This is an ambitious
study in the planning phases to try to
assess a broad array of psychiatric, psy-
chological, metabolic, and cardiovascular risk factors in a large sample of large sib-
ships including parents, ascertained using population-based registries in
Finland.(Dr. Kenneth Kendler)
5. Study of Genotype Environment Interactions
In collaboration with Drs. Lindon Eaves, Kenneth Kendler and others, we are plan-
ning a research initiative to do a large scale study of genotype environment interac-
tions using our well characterized population-based twin registries. This project will
begin by obtaining high quality DNA from blood samples and analyzed using a vari-
ety of sophisticated methods including quite high quality environmental measures
to try to clarify the interrelationship of specified genetic and environmental risk fac-
tors in the etiology of psychiatric and substance use disorders.
Psychiatric and Behavioral
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