missing heritability
Shi H, Kichaev G & Pasaniuc B 2016 Contrasting the genetic architecture of 30 complex traits from summary association data. Am J Hum Genet 99:139-153.
- a fraction of the missing heritability is due to multiple causal variants or poor tagging of hidden causal variants at known risk loci
- we sought to quantify the variability in polygenicity across traits
- for highly polygenic traits, we expected the cumulative fraction of total SNP heritability to be proportional to the fraction of genome covered
- whereas for less polygenic traits, we expected to see a small genomic fraction accounting for a large fraction of the total SNP heritability
- in SCZ and height, the top 1% of loci with the highest local SNP heritability contributed to 4.2% (SE = 1.0%) and 6.5% (SE = 1.5%), respectively, of the total SNP heritability of these traits
- at the other extremes, RA and lipid traits (HDL, LDL, TC, and TG) had a lower degree of polygenicity
- the top 1% of loci accounted for 14%–30% of the total SNP heritability
- the different degrees of polygenic signals across traits reflect both a difference in disease architecture (i.e., distribution of effect sizes) and a difference in the sample sizes for the GWAS summary data
