PT - JOURNAL ARTICLE AU - Farhad Hormozdiari AU - Anthony Zhu AU - Gleb Kichaev AU - Ayellet V. Segré AU - Chelsea J.-T. Ju AU - Jong Wha Joo AU - Hyejung Won AU - Sriram Sankararaman AU - Bogdan Pasaniuc AU - Sagiv Shiffman AU - Eleazar Eskin TI - Widespread allelic heterogeneity in complex traits AID - 10.1101/076984 DP - 2016 Jan 01 TA - bioRxiv PG - 076984 4099 - http://biorxiv.org/content/early/2016/09/22/076984.short 4100 - http://biorxiv.org/content/early/2016/09/22/076984.full 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.