Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche
Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche
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DOI：
10.1038/ng.383
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发表时间：
2009-06-01
期刊：
影响因子：
30.8
通讯作者：
Stefansson, Kari
中科院分区：
文献类型：
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作者：
Sulem, Patrick;Gudbjartsson, Daniel F.;Stefansson, Kari
初潮早与成人身高较短（1）和儿童期体脂较高（2）相关。我们对15，297名冰岛女性进行了月经初潮年龄（AAM）的全基因组关联研究。对来自冰岛、丹麦和荷兰（N = 10，040）的复制集进行的联合分析显示，6q21上靠近LIN28 B基因的rs314280 [T]与AAM之间存在显著关联（每个等位基因的效应= 1.2个月后; P = 1.8 x 10（-14））。同一连锁不平衡（LD）区块内的第二个SNP rs314277将rs314280 [T]分成具有不同效应的两个单倍型（每个等位基因0.9个月和1.9个月）。这些变体与更高的成年身高有关（3，4）。与成人身高的相关性不能解释与AAM的相关性，反之亦然。以前与身高相关的其他变异（3 - 5）与AAM无显著相关性。鉴于体脂与AAM之间的联系，我们还评估了最近与较高体重指数（BMI）（6 - 11）相关的11种变异和与早期AAM相关的5种变异。
Earlier menarche correlates with shorter adult height(1) and higher childhood body fat(2). We conducted a genome-wide association study of age at menarche (AAM) on 15,297 Icelandic women. Combined analysis with replication sets from Iceland, Denmark and the Netherlands (N = 10,040) yielded a significant association between rs314280[T] on 6q21, near the LIN28B gene, and AAM (effect = 1.2 months later per allele; P = 1.8 x 10(-14)). A second SNP within the same linkage disequilibrium (LD) block, rs314277, splits rs314280[T] into two haplotypes with different effects (0.9 months and 1.9 months per allele). These variants have been associated with greater adult height(3,4). The association with adult height did not account for the association with AAM or vice versa. Other variants, previously associated with height(3-5), did not associate significantly with AAM. Given the link between body fat and AAM, we also assessed 11 variants recently associated with higher body mass index (BMI)(6-11) and 5 of those associated with earlier AAM.