A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci

被引：199

作者：

Hinds, David A. ^{[1
]}

McMahon, George ^{[2
]}

Kiefer, Amy K. ^{[1
]}

Do, Chuong B. ^{[1
]}

Eriksson, Nicholas ^{[1
]}

Evans, David M. ^{[2
]}

St Pourcain, Beate ^{[3
]}

Ring, Susan M. ^{[3
]}

Mountain, Joanna L. ^{[1
]}

Francke, Uta ^{[1
]}

Davey-Smith, George ^{[2
]}

Timpson, Nicholas J. ^{[2
]}

Tung, Joyce Y. ^{[1
]}

机构：

[1] 23andMe Inc, Mountain View, CA USA

[2] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Sch Social & Community Med, Bristol, Avon, England

[3] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England

来源：

NATURE GENETICS | 2013年 / 45卷 / 08期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

GENOTYPE DATA; RISK LOCI; T-CELLS; ASTHMA; VARIANTS; GENE; DIFFERENTIATION; POPULATION; RESPONSES; HERITABILITY;

D O I：

10.1038/ng.2686

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association P < 5 x 10(-8), including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P = 5.3 x 10(-21)); 6p21.33 near HLA-C and MICA (rs9266772, P = 3.2 x 10(-12)); 5p13.1 near PTGER4 (rs7720838, P = 8.2 x 10(-11)); 2q33.1 in PLCL1 (rs10497813, P = 6.1 x 10(-10)), 3q28 in LPP (rs9860547, P = 1.2 x 10(-9)); 20q13.2 in NFATC2 (rs6021270, P = 6.9 x 10(-9)), 4q27 in ADAD1 (rs17388568, P = 3.9 x 10(-8)); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P = 4.8 x 10(-8)). We identified one locus with substantial evidence of differences in effects across allergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P = 1.7 x 10(-12)), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease.

引用

页码：907 / U292

页数：7

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