Jian Yang1.*, Taeheon Lee2, Jaemin Kim3, Myeong-Chan Cho4, Bok-Ghee Han4, Jong-Young Lee4, Hyun-Jeong Lee5, Seoae Cho6, Heebal Kim2,3,6*
1 University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia, 2 Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea, 3 Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Korea, 4 Center for Genome Science, Korea National Institute of Health, Osong Health Technology, Chungcheongbuk-do, Korea, 5 Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration, Suwon, Korea, 6 C&K Genomics, Seoul, Korea
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 (h2G). On average across 47 of the 49 traits for which the estimate of h2G is non-zero, common SNPs explain approximately one-third (range of 7.8% to 76.8%) of narrow sense heritability. The estimate of is h2G 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.