RT Journal Article SR Electronic T1 Widespread allelic heterogeneity in complex traits JF bioRxiv FD Cold Spring Harbor Laboratory SP 076984 DO 10.1101/076984 A1 Farhad Hormozdiari A1 Anthony Zhu A1 Gleb Kichaev A1 Ayellet V. Segrè A1 Chelsea J.-T. Ju A1 Jong Wha Joo A1 Hyejung Won A1 Sriram Sankararaman A1 Bogdan Pasaniuc A1 Sagiv Shifman A1 Eleazar Eskin YR 2016 UL http://biorxiv.org/content/early/2016/11/27/076984.abstract AB Recent successes in genome-wide association studies (GWAS) make it possible to address important questions about the genetic architecture of complex traits, such as allele frequency and effect size. One lesser-known aspect of complex traits is the extent of allelic heterogeneity (AH) arising from multiple causal variants at a locus. We developed a computational method to infer the probability of AH and applied it to three GWAS and four expression quantitative trait loci (eQTL) datasets. We identified a total of 4152 loci with strong evidence of AH. The proportion of all loci with identified AH is 4-23% in eQTLs, 35% in GWAS of High-Density Lipoprotein (HDL), and 23% in schizophrenia. For eQTL, we observed a strong correlation between sample size and the proportion of loci with AH (R2=0.85, P = 2.2e-16), indicating that statistical power prevents identification of AH in other loci. Understanding the extent of AH may guide the development of new methods for fine mapping and association mapping of complex traits.