23andMe, Inc., Mountain View, California, USA.
Nat Genet. 2013 Aug;45(8):907-11. doi: 10.1038/ng.2686. Epub 2013 Jun 30.
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<5×10(-8), including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P=5.3×10(-21)); 6p21.33 near HLA-C and MICA (rs9266772, P=3.2×10(-12)); 5p13.1 near PTGER4 (rs7720838, P=8.2×10(-11)); 2q33.1 in PLCL1 (rs10497813, P=6.1×10(-10)), 3q28 in LPP (rs9860547, P=1.2×10(-9)); 20q13.2 in NFATC2 (rs6021270, P=6.9×10(-9)), 4q27 in ADAD1 (rs17388568, P=3.9×10(-8)); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P=4.8×10(-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=1.7×10(-12)), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease.
过敏疾病非常普遍，给公共卫生带来了巨大负担。我们对 53862 名个体的自我报告的猫、尘螨和花粉过敏的全基因组关联进行了荟萃分析。我们使用广义估计方程来对共同和过敏特异性遗传效应进行建模。我们确定了 16 个具有关联性的共同易感性位点，关联 P 值均小于 5×10(-8)，其中包括 8 个先前与哮喘相关的位点，以及位于 4p14 附近的 TLR1、TLR6 和 TLR10（rs2101521，P=5.3×10(-21)）；6p21.33 附近的 HLA-C 和 MICA（rs9266772，P=3.2×10(-12)）；5p13.1 附近的 PTGER4（rs7720838，P=8.2×10(-11)）；2q33.1 附近的 PLCL1（rs10497813，P=6.1×10(-10)），3q28 附近的 LPP（rs9860547，P=1.2×10(-9)）；20q13.2 附近的 NFATC2（rs6021270，P=6.9×10(-9)），4q27 附近的 ADAD1（rs17388568，P=3.9×10(-8)）；以及 14q21.1 附近的 FOXA1 和 TTC6（rs1998359，P=4.8×10(-8)）。我们在人类白细胞抗原（HLA）Ⅱ类区域的 6p21.32 鉴定出一个具有明显跨过敏效应差异证据的位点（rs17533090，P=1.7×10(-12)），该位点与猫过敏强烈相关。我们的研究为免疫和自身免疫性疾病的共同病因提供了新的见解。
