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THE GENETIC ARCHITECTURES OF PSYCHOLOGICAL TRAITS

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THE GENETIC ARCHITECTURES OF PSYCHOLOGICAL TRAITS

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THE GENETIC ARCHITECTURES OF PSYCHOLOGICAL TRAITS

  1. 1. THE GENETIC ARCHITECTURES OF PSYCHOLOGICAL TRAITS James J. Lee University of Minnesota Twin Cities
  2. 2. THREE LAWS OF BEHAVIOR GENETICS • First Law. All behavioral traits are heritable. • Second Law. The effect of being raised in the same family is smaller than the effect of genes. • Third Law. A substantial portion of the variance in behavioral traits is not accounted for by genes or families. Eric Turkheimer, the coiner of the Three Laws of Behavior Genetics.
  3. 3. EVIDENCE FROM CLASSICAL QUANTITATIVE GENETICS 90 100 110 120 130 The Minnesota Adolescent Adoption Study (Scarr & Weinberg, 1978; Scarr, 1997) 80 90 100 110 120 130 BIOLOGICAL FAMILIES MIDPARENT IQ OFFSPRING IQ β = 0.61± 0.07 90 100 110 120 130 80 90 100 110 120 130 ADOPTIVE FAMILIES MIDPARENT IQ OFFSPRING IQ β = 0.13 ± 0.08
  4. 4. EVIDENCE FROM CLASSICAL QUANTITATIVE GENETICS BIOLOGICAL FAMILIES ADOPTIVE FAMILIES The Sibling Interaction and Behavior Study (McGue et al., 2007)
  5. 5. THE SEARCH FOR CAUSAL VARIANTS AT THE DNA LEVEL • If studies of twins and other kinships support the Three Laws, it seems justified to search for the causal loci at the DNA level. • This is the aim of genome-wide association studies (GWAS). A research subject provides DNA by spitting into a tube with a preservative.
  6. 6. BACKLASH AGAINST GWAS OF PSYCHOLOGICAL TRAITS • Correlations between common variants and phenotypes such as general cognitive ability (g) and schizophrenia have turned out to be very small. • We have just reported three common SNPs that each account for ~0.02% of IQ variance (Rietveld et al., 2014).
  7. 7. BACKLASH AGAINST GWAS OF PSYCHOLOGICAL TRAITS • In response, a fellow at the Center for Genetics and Society wrote a blog post called “The Stupidity of Smart Genes.” • Some academics are scarcely more charitable. Kevin Mitchell of Trinity College Dublin: “The idea that this trait is determined by common variants … is really unproven.”
  8. 8. MY RESPONSE TO THE BACKLASH • We seem to have a paradox: if traits are as heritable as implied by classical studies, then where are the genes? • I argue that the heritability is hiding in plain sight: there are thousands of causal variants, each of which exerts a small effect—which means that it is difficult to find any single one.
  9. 9. MY RESPONSE TO THE BACKLASH • I provide an estimate of the total GWAS sample size required to capture the entire heritability (due to common variants) of a phenotype like g. • Most importantly, I argue that chasing down thousands of DNA variants with small effects is a worthy scientific enterprise.
  10. 10. HERITABILITY ESTIMATED DIRECTLY FROM DNA DATA • A critic might claim that GWAS of psychological traits cannot be guaranteed to produce more “hits” as sample size grows. • Perhaps “indirect” heritability estimates from studies of twins, adoptees, etc. are flawed and there are not that many causal loci after all. Richard Nixon and Forrest Gump may be slightly less similar at the DNA level than most other random pairs of people.
  11. 11. HERITABILITY ESTIMATED DIRECTLY FROM DNA DATA • In recent years a new method, often called GCTA (after the software package Genome-wide Complex Trait Analysis), obtains “direct” estimates of heritability from DNA data. • Think of two people who are not related to you. Richard Nixon and Forrest Gump may be slightly less similar at the DNA level than most other random pairs of people.
  12. 12. HERITABILITY ESTIMATED DIRECTLY FROM DNA DATA • If we genotype/sequence all three individuals, you will turn out by chance to be slightly more similar at the genetic level to person A than to person B. • Are you also phenotypically more similar to A than to B? Richard Nixon and Forrest Gump may be slightly less similar at the DNA level than most other random pairs of people.
  13. 13. HERITABILITY ESTIMATED DIRECTLY FROM DNA DATA • In a large sample of unrelated people, we look at all pairs of people and calculate their genetic and phenotypic similarities. • Higher heritability means that genetically similar people will tend to be phenotypically similar. Richard Nixon and Forrest Gump may be slightly less similar at the DNA level than most other random pairs of people.
  14. 14. HERITABILITY ESTIMATED DIRECTLY FROM DNA DATA E (yy0) = A

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