Ubiquitous Polygenicity of Human Complex Traits: Genome-Wide Analysis of 49 Traits in Koreans

Recent studies in population of European ancestry have shown that 30%~50% of heritability for human complex traits such as height and body mass index, and common diseases such as schizophrenia and rheumatoid arthritis, can be captured by common SNPs and that genetic variation attributed to chromosomes are in proportion to their length. Using genome-wide estimation and partitioning approaches, we analysed 49 human quantitative traits, many of which are relevant to human diseases, in 7,170 unrelated Korean individuals genotyped on 326,262 SNPs. For 43 of the 49 traits, we estimated a nominally significant (P<0.05) proportion of variance explained by all SNPs on the Affymetrix 5.0 genotyping array (). On average across 47 of the 49 traits for which the estimate of is non-zero, common SNPs explain approximately one-third (range of 7.8% to 76.8%) of narrow sense heritability. The estimate of is highly correlated with the proportion of SNPs with association P<0.031 (r2 = 0.92). Longer genomic segments tend to explain more phenotypic variation, with a correlation of 0.78 between the estimate of variance explained by individual chromosomes and their physical length, and 1% of the genome explains approximately 1% of the genetic variance. Despite the fact that there are a few SNPs with large effects for some traits, these results suggest that polygenicity is ubiquitous for most human complex traits and that a substantial proportion of the “missing heritability” is captured by common SNPs. The “missing heritability” problem has been intensely debated for the last few years. Possible explanations include the existence of many genetic variants each with a small effect, rare variants with large effects, and heritability being over-estimated. Previous studies using whole-genome estimation have demonstrated that for human complex traits such as height, body mass index, and intelligence, a large portion of the heritability can be captured by all the common SNPs on the current genotyping arrays. These studies, however, were all concentrated only on a few traits. In this study, we analysed 49 quantitative traits in a sample of ~7,000 unrelated Korean individuals. We found that, on average over all the traits, common SNPs on the Affymetrix 5.0 genotyping array explain approximately a third of the heritability, that genetic variants are widely distributed across the whole genome with longer chromosomes explaining more phenotypic variation, and that approximately any 1% of the genome explains 1% of the heritability. Despite examples where a few variants explain a substantial amount of variation, all these results are consistent with polygenicity being ubiquitous for most complex traits.