Widespread Allelic Heterogeneity in Complex Traits

被引：51

作者：

Hormozdiari, Farhad ^{[1
,2
]}

Zhu, Anthony ^{[1
]}

Kichaev, Gleb ^{[3
]}

Ju, Chelsea J. -T. ^{[1
]}

Segre, Ayellet V. ^{[4
,5
]}

Joo, Jong Wha J. ^{[1
,6
]}

Won, Hyejung ^{[7
]}

Sankararaman, Sriram ^{[1
,8
]}

Pasaniuc, Bogdan ^{[8
,9
,10
]}

Shifman, Sagiv ^{[8
,11
]}

Eskin, Eleazar ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA

[2] Harvard TH Chan Sch Pub lic Hlth, Dept Epidemiol, Boston, MA 02115 USA

[3] Univ Calif Los Angeles, Bioinformat IDP, Los Angeles, CA 90095 USA

[4] MIT, Broad Inst, Canc Program, Cambridge, MA 02142 USA

[5] Harvard Univ, Cambridge, MA 02142 USA

[6] Dongguk Univ Seoul, Dept Comp Sci Engn, Seoul 04620, South Korea

[7] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Neurogenet Program, Los Angeles, CA 90095 USA

[8] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA

[9] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90095 USA

[10] Univ Calif Los Angeles, Lab Med, Los Angeles, CA 90095 USA

[11] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2017年 / 100卷 / 05期

基金：

美国国家科学基金会; 以色列科学基金会;

关键词：

GENOME-WIDE ASSOCIATION; MIXED-MODEL ANALYSIS; INCREASING POWER; GENETIC-VARIANTS; LOCI; GWAS; IDENTIFICATION; COLOCALIZATION; EXPRESSION; SIGNALS;

D O I：

10.1016/j.ajhg.2017.04.005

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Recent successes in genome-wide association studies (GWASs) 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 GWASs and four expression quantitative trait loci (eQTL) datasets. We identified a total of 4,152 loci with strong evidence of AH. The proportion of all loci with identified AH is 4%-23% in eQTLs, 35% in GWASs of high-density lipoprotein (HDL), and 23% in GWASs of schizophrenia. For eQTLs, we observed a strong correlation between sample size and the proportion of loci with AH (R-2 = 0.85, p = 2.2 x 10(-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.

引用

页码：789 / 802

页数：14

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