Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium.
Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium.
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儿童基因-环境相互作用以及与屈光不正和近视相关的遗传变异的年龄依赖性影响：CREAM 联盟
DOI：
10.1038/srep25853
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发表时间：
2016-05-13
影响因子：
4.6
通讯作者：
CREAM Consortium
中科院分区：
文献类型：
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作者：
Fan Q;Guo X;Tideman JW;Williams KM;Yazar S;Hosseini SM;Howe LD;Pourcain BS;Evans DM;Timpson NJ;McMahon G;Hysi PG;Krapohl E;Wang YX;Jonas JB;Baird PN;Wang JJ;Cheng CY;Teo YY;Wong TY;Ding X;Wojciechowski R;Young TL;Pärssinen O;Oexle K;Pfeiffer N;Bailey-Wilson JE;Paterson AD;Klaver CC;Plomin R;Hammond CJ;Mackey DA;He M;Saw SM;Williams C;Guggenheim JA;CREAM Consortium
目前在东亚流行的近视是造成无法治愈的视力障碍的主要原因。成人全基因组关联研究（GWAS）已经确定了39个与屈光不正和近视相关的基因座。在这里，研究人员对5200名7-15岁的儿童进行了纵向评估，研究了这39个基因位点的遗传变异与屈光不正的发病年龄之间的关系，以及涉及主要环境风险因素、附近工作和户外活动时间的基因-环境相互作用。特定的变异可以分类为显示以下证据：(a)早发效应在童年时期保持稳定，(b)早发效应随着年龄的增长而进一步发展，或(c)在童年后期发病（N = 10、5和11个变异）。所有39种变异的遗传风险评分（GRS）分别解释了7岁和15岁屈光不正变异的0.6% （P = 6.60 e - 08）和2.3% (P = 6.9E-21)，支持这些遗传变异在年龄较大时的影响增加。在多祖先样本（合计N = 5599）中进行复制，获得了亚洲人和欧洲人共有的12种变异中的6种在儿童时期发病的证据。没有迹象表明变异或GRS效应会随着户外时间的变化而改变，但有5个变异显示出与附近工作相互作用的名义证据（顶部变异，rs7829127 inZMAT4; P = 6.30 e - 04）。
Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7–15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E–08) and 2.3% (P = 6.9E–21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 inZMAT4; P = 6.3E–04).