Family Phenotyping Studies


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Family Phenotyping Studies – Mark Leppert, PhD; Distinguished Professor of Human
Genetics in the Department of Human Genetics, University of Utah School of Medicine

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  • Update with both names
  • This uses all individuals with birth years. The 1980’s bar is shorter than 1970’s because individuals who moved to Utah and do not have a driver license are not yet included in the UPDB e.g. those born in 1988 and 1989. Utah had more births in the 1980s than in the 1970s – so that is not the difference in the bars. We are currently linking the 2005 birth certifications and it will be updated.
  • For example, 432,761 individuals born from 1950-59 are in multi-generation families with 168,267 in two generation families and 264,494 in families with three or more generations.
  • There are 8 generations in UPDB; the first 6 generations are from genealogy records and the last two from Utah birth certificates. Since death records begin in 1904—we know the cause of death of 6 individuals in the 3 rd generation.
  • This pedigree has been trimmed to show individuals with cancer or polyps. The full pedigree includes 931 family members and 7 generations. The age of diagnosis is shown for cancer (red). DC means colon cancer diagnosis prior to 1966 and from death certificate.
  • These are cancer percentages 25% to one third for HCI, 60% for Intermountain
  • Family Phenotyping Studies

    1. 1. Mark Leppert, Ph.D Department of Human Genetics, University of Utah, Salt Lake City, Utah Family Phenotyping Studies October 14, 2010
    2. 2. Why Does Utah Provide a Unique Genetic Resource? Large Families Plus High Quality Clinical Information are Critical to Provide Insight into the Genetic Variations that Cause Disease
    3. 3. Utah Population Database (UPDB) <ul><li>University of Utah research resource </li></ul><ul><li>Over 30 years of research </li></ul><ul><li>About 14 million documents </li></ul><ul><li>65 approved projects </li></ul>
    4. 4. UPDB Resource <ul><li>Family histories (mainly Utah and SE Idaho families) </li></ul><ul><ul><li>Genealogies: Records from Family History Library, maintained by </li></ul></ul><ul><ul><li>Church of Jesus Christ of Latter-day Saints </li></ul></ul><ul><ul><li>Family reconstitution: Create families from Utah’s vital records: birth, marriage and death </li></ul></ul><ul><ul><ul><li>Create maternal and paternal birth histories </li></ul></ul></ul><ul><ul><li>Link across generations - 10 generations for some families </li></ul></ul><ul><li>Medical information is linked to family histories </li></ul><ul><ul><li>State wide cancer records </li></ul></ul><ul><ul><li>Vital records: cause of death and medical details from birth certificates </li></ul></ul><ul><ul><li>University of Utah Health Sciences medical records </li></ul></ul>
    5. 5. UPDB – 5.45 million individuals by 10-year birth cohorts from about 1740 to 2004
    6. 6. UPDB – 3.84 million individuals In families of two to ten generations by 10-year birth cohorts from about 1740 to 2004
    7. 7. M F 10 2 7 3 12 8 4 1 5 Father (F), Mother (M) and children by birth order Married 1853, 12 children, 3 infant deaths Utah Family, Circa 1900
    8. 8. Utah Family in UPDB <ul><li>Spans 10 generations from 1807 to 2004 </li></ul><ul><li>Couple (in picture): 4,021 descendants (3,567 living) </li></ul><ul><li>Paternal side: 6,146 descendants (5,377 living) </li></ul><ul><li>Maternal side: 16,337 descendants (14,284 living) </li></ul>8 th of 15 children 1 st of 5 children 1807 1802 1817 1819 1889 1870 1854 1850 Canada New York England Connecticut M F 1837 1835 1917 1915 1 2 3 4 5 6 7 8 9 10 11 12 1854 1855 1857 1859 1861 1863 1864 1867 1869 1870 1872 1874 1932 1940 1930 1931 1892 1863 1939 1952 1869 1902 1872 1943 8 th of 15 children 1 st of 5 children 1807 1802 1817 1819 1889 1870 1854 1850 Canada New York England Connecticut M F 1837 1835 1917 1915 1 2 3 4 5 6 7 8 9 10 11 12 1854 1855 1857 1859 1861 1863 1864 1867 1869 1870 1872 1874 1932 1940 1930 1931 1892 1863 1939 1952 1869 1902 1872 1943
    9. 9. Extraordinary Research Opportunity <ul><li>Maintain longitudinal data - Across individual’s lifetime and generations </li></ul><ul><li>Merge genetics with demography – Utah population 2,784,572 (2009) </li></ul><ul><li>Conduct studies that analyze familial data </li></ul><ul><ul><li>Identify large families with affected members where genetic relationships are known </li></ul></ul><ul><ul><li>Look for predisposition to disease </li></ul></ul><ul><li>Low inbreeding rate </li></ul><ul><ul><li>Large initial founding population </li></ul></ul><ul><ul><li>High rates of immigration from diverse outside populations </li></ul></ul><ul><li>Extrapolate findings to broad spectrum of US and Western and Northern European populations </li></ul>
    10. 10. Sources of Medical Information <ul><li>Merged into UPDB </li></ul><ul><li>Utah and Idaho state-wide cancer registries </li></ul><ul><li>Cause of death on Utah death certificates </li></ul><ul><li>Birth details on Utah birth certificates </li></ul><ul><li>Utah birth defects registry </li></ul><ul><li>Linked to UPDB </li></ul><ul><li>U of U Health Sciences Center (UUHS), Enterprise data warehouse </li></ul><ul><li>Intermountain Health Care, Enterprise data warehouse </li></ul>
    11. 11. Examples of Types of Studies <ul><ul><li>Cancer Studies </li></ul></ul><ul><ul><ul><li>Cancer genetics: breast, colon, melanoma, pancreas, prostate </li></ul></ul></ul><ul><ul><ul><li>Familial aggregation of cancers </li></ul></ul></ul><ul><ul><li>Obstetric complications and childhood studies </li></ul></ul><ul><ul><ul><li>Preeclampsia and preterm births </li></ul></ul></ul><ul><ul><ul><li>Birth defects, autism, juvenile idiopathic arthritis </li></ul></ul></ul><ul><ul><li>Chronic and other diseases and conditions </li></ul></ul><ul><ul><ul><li>Diabetes, psoriasis, rheumatoid arthritis, inflammatory bowel disease </li></ul></ul></ul><ul><ul><ul><li>Macular degeneration, interstitial lung disease, mullerian anomalies, chronic pain, aneurysms </li></ul></ul></ul><ul><ul><li>Aging and mortality </li></ul></ul><ul><ul><ul><li>Longevity </li></ul></ul></ul><ul><ul><ul><li>Memory in aging and Alzheimer’s Disease </li></ul></ul></ul>
    12. 12. High Risk Colon Family Ascertained from Cancer High Risk Clinic DC 73 65 63 84 DC 68 2 sibs 5 sibs 64 59 56 b. 1865 b. 1864 Prostate This pedigree has been trimmed to show individuals with cancer and precancerous polyps. The full pedigree includes 931 family members and 7 generations
    13. 13. Statewide Research Network 85% of state 25% of state 60% of state Intermountain Healthcare Huntsman Cancer Institute Fraction of state population served
    14. 14. <ul><li>16 cancer centers, clinics and education centers </li></ul><ul><li>210 participating cancer physicians </li></ul><ul><li>Sites serve all major population, </li></ul><ul><li>rural and frontier areas </li></ul><ul><li>Thus, outcome studies and clinical trials now possible statewide and </li></ul><ul><li>in underserved groups </li></ul>
    15. 15. Additional High Risk Clinics <ul><li>Many clinics have extensive, greater than 10 years, longitudinal data </li></ul><ul><li>Many clinics have large collections of banked biosamples </li></ul><ul><li>Many clinics are increasingly collecting brain images and expression data </li></ul><ul><li>Other clinics include: asthma, juvenile rheumatoid arthritis, COPD, multiple sclerosis, muscular dystrophy, autism, coronary heart disease, hypertension, alzheimer’s disease, recurrent miscarriages </li></ul>
    16. 16. Environmental <ul><li>Census (1880-1930) </li></ul><ul><ul><li>Individual and Household Level, Neighborhoods </li></ul></ul><ul><ul><li>Occupation, wealth, literacy, education </li></ul></ul><ul><li>Geo-coded in UPDB </li></ul><ul><li>Geographic Information Systems </li></ul><ul><ul><li>Spatial data </li></ul></ul><ul><ul><li>E.g., Water/air quality, Toxins, Proximity to health care </li></ul></ul><ul><ul><li>Walkability </li></ul></ul>
    17. 17. Utah Population Database Genealogies (Family History Library) Vital Records (Births, Deaths/Fetal Marriages, Divorces) Utah Department of Health Cancer Records (Utah Cancer Registry, Cancer Data Registry of Idaho) Utah Inpatient Hospital Claims (Utah Dept of Health) University of Utah Health Sciences Center Intermountain Healthcare Center for Medicare and Medicaid Studies Social Security Death Records Driver Licenses (Utah Department of Public Safety) Utah Voter Registration
    18. 18. Records in UPDB RECORD TYPE RECORDS Family History Records 1,608,131 1880 Census 142,711 Birth Certificates (1915-21, 1947-2008) 2,309,408 Marriage Certificates (1978-2008) 642,080 Divorce Records (1978-2008) 278,629 Death Certificates (1904-2008) 751,343 Fetal Deaths (1978-2008) 8,425 Social Security Death Index 479,491 Utah Cancer Records (1966-2007) 255,516 Idaho Cancer Records (1969-2007) 135,816 Driver License 3,060,281 Inpatient Hospital Claims (1996-2008) 3,284,454 Voter Registration 1,586,962 TOTAL RECORDS 14.1 million LINKS TO EXTERNAL RECORD SETS University of Utah Health Sciences Center 1,375,673 Intermountain Healthcare 3,429,337 Medicare Claims 25,666,447
    19. 19. Security and Confidentiality <ul><li>Not a public database – for research only </li></ul><ul><ul><li>Researchers have no electronic access to identifying information </li></ul></ul><ul><li>State of the art database </li></ul><ul><li>Policies and procedures on confidentiality </li></ul><ul><ul><li>All projects are reviewed by IRB and data contributions </li></ul></ul><ul><li>Require researchers to sign confidentiality agreements </li></ul><ul><li>Contact of potential subjects by an appropriate third party </li></ul><ul><li>Wylie and Mineau, Biomedical databases: protecting privacy and promoting research. </li></ul><ul><li>Trends in Biotechnology, March, 2003. </li></ul>
    20. 20. Recruitment of Subjects <ul><li>Contact of potential subjects by an appropriate third party </li></ul><ul><ul><li>For cancer studies, contact by the Utah Cancer Registry </li></ul></ul><ul><ul><li>For studies using University of Utah Health Sciences records </li></ul></ul><ul><ul><ul><li>A investigator/physician can contact his own patients with IRB approval </li></ul></ul></ul><ul><ul><ul><li>Otherwise RGE contacts patients </li></ul></ul></ul><ul><ul><li>For studies using Utah vital records or DLD </li></ul></ul><ul><ul><ul><li>RGE contacts subjects </li></ul></ul></ul><ul><li>Letter is sent to individuals explaining study and asking permission to give their contact information to researcher </li></ul>
    21. 21. Administration for UPDB <ul><ul><li>Utah Resource for Genetic and Epidemiologic Research </li></ul></ul><ul><ul><li> </li></ul></ul><ul><li>1982 Executive Order of Governor established RGE </li></ul><ul><ul><li>A data resource for the collection, storage, study and dissemination of medical and related information and for the purpose of reducing morbidity </li></ul></ul><ul><li>2003 Utah State Code 26-15, modified to increase confidentiality of familial and other information </li></ul><ul><li>RGE reports to Associate Vice President for Research, University of Utah </li></ul>
    22. 22. PPR, RGE, Informatics <ul><li>Ken R. Smith, Ph.D. Director, PPR </li></ul><ul><li>Geraldine P. Mineau, Ph.D. Associate Director, PPR </li></ul><ul><li>Karen Curtin, Ph.D. Genetic Epidemiologist </li></ul><ul><li>PPR Staff: HCI Informatics Staff: </li></ul><ul><li>Alison Fraser, MSPH Cindy Spigle, BACS </li></ul><ul><li>Diana Lane Reed, CCRP </li></ul><ul><li>Carole Schaefer, BACS   Dinny Berry, MS </li></ul><ul><li>Richard Pimentel, MSCS Robb Cundick, PhD </li></ul><ul><li>Andy Hammer, BSCS Cody Haroldsen, BACS </li></ul><ul><li>Emily Smith, MA </li></ul><ul><li>Solange Gomes, BA </li></ul><ul><li>Alex Glazier </li></ul><ul><li>Eva Bell </li></ul><ul><li>Jahn Barlow, MPA – Director, Utah Resource of Genetic and Epidemiologic Research </li></ul>