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Psychiatric Genetics Study Summary
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Summary of the second minor course, based on the learning objectives.
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Study Summary – Learning Objectives Psychiatric Genetics (Minor Course 2) Can explain the concept of (missing) heritability and interpret heritability
estimates of psychiatric disorders
Heritability – the percentage of phenotypic variation (var(p)) that is explained by genetic
variation; quantification (0-1) how much of a trait can be explained by genetics. Defined for
each population and in each set of environments; not individuals.
- A heritability of 0.4 means that about 40% of the individual differences that we
observe in the population may be attributed to genetic individual differences.
- If all variation in phenotype is due to genetic variation, h2 = 1.
- If no variation in phenotype is due to genetic variation, h2 = 0.
- A high heritability doesn’t mean that a trait is unaffected by its environment. If the
environment is changed, there may be large differences in phenotype.
- Typically the same in men and women. Can change over time due to changes in
environmental factors or between age cohorts.
o i.e. In children, the environmental factors play a larger role in their IQ IQ is
more heritable in adults than children.
Co-heritability – concept to describe the genetic associations within pairs of quantitative
traits; a similar measure to quantify genetic overlap.
- The square of the genetic correlation (0-1, slightly different scale)
- SNP-based
For many highly heritable disorders GWAS hits explain only a fraction of the heritability
(typically several % of the phenotypic variation at most).
- Stringent multiple testing thresholds (= many small effects not detected)
- Thousands of sub-threshold effects are expected to exist
- All small effects together explain a larger portion of the heritability
Twin-based heritability – heritability investigated by comparing phenotypes of twins that are
genetically similar. Twin studies are done to investigate the correlation between genetic and
environmental factors in a phenotype (i.e. disease).
SNP-based heritability – phenotypic variation explained by SNPs in genetic variation.
A single genetic variation cannot account for much of the heritability of a phenotype. Twin
studies attempt to find phenotypical variation due to genetic variants high percentages of
heritability. GWASes search for loci which are effected/different and have a higher threshold
more stringent.
- Twin studies produce a high heritability, much larger than the amount of explained
heritability from a GWAS missing heritability.
Missing heritability – discrepancy between twin-based heritability and GWAS-heritability;
heritability that isn’t explained by GWAS-hits but noticed in a population.
Largely explained by polygenicity of many disorders.
- There are many variants with smaller effects. Solution: larger sample size
- Rare variants that are not present on arrays, due to small sample sizes of
insufficiently large arrays. Solution: pooling.
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