Using Y-Chromosomal Haplogroups in Genetic Association Studies and Suggested Implications.
Using Y-Chromosomal Haplogroups in Genetic Association Studies and Suggested Implications.
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DOI：
10.3390/genes9010045
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发表时间：
2018-01-22
期刊：
影响因子：
3.5
通讯作者：
Rodriguez S
中科院分区：
文献类型：
--
作者：
Erzurumluoglu AM;Baird D;Richardson TG;Timpson NJ;Rodriguez S
Y染色体(Y-DNA)单倍群在群体遗传学中的应用比在遗传流行病学中更广泛，尽管Y-DNA单倍群与包括心脏代谢特性在内的几个性状之间的关联已有报道。在主成分分析确定的明显同质的群体中，仍然存在Y-DNA单倍群变异，这将是群体历史的结果。因此，Y-DNA单倍群可能存在隐藏的层积和/或不同的表型效应。为了验证这一点，我们假设，在测试常染色体单核苷酸多态(SNPs)和表型之间的关联之前，根据Y-DNA单群对个体进行分层会产生关联的差异。为了验证概念，我们从两个流行病学队列--雅芳亲子纵向研究(ALSPAC)(n=5080；816个Y-DNA SNPs)和1958年出生队列(n=1457；1849个Y-DNA SNPs)--中提取了6537名男性的Y-DNA单倍群，并研究了32个SNPs与体重指数(BMI)之间的密切关联，包括肥胖相关蛋白(FTO)和肥胖相关蛋白(FTO)中或附近的SNPs。总体而言，当考虑Y-DNA单倍群时，两个队列中没有复制关联，这表明，至少对于BMI来说，几乎没有证据表明Y-DNA结构在表型或SNP关联上存在差异。使用其他性状、表型全关联研究(Phewas)、其他单群和/或常染色体SNPs进行进一步研究，以测试该方法的普适性和实用性。
Y-chromosomal (Y-DNA) haplogroups are more widely used in population genetics than in genetic epidemiology, although associations between Y-DNA haplogroups and several traits, including cardiometabolic traits, have been reported. In apparently homogeneous populations defined by principal component analyses, there is still Y-DNA haplogroup variation which will result from population history. Therefore, hidden stratification and/or differential phenotypic effects by Y-DNA haplogroups could exist. To test this, we hypothesised that stratifying individuals according to their Y-DNA haplogroups before testing for associations between autosomal single nucleotide polymorphisms (SNPs) and phenotypes will yield difference in association. For proof of concept, we derived Y-DNA haplogroups from 6537 males from two epidemiological cohorts, Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 5080; 816 Y-DNA SNPs) and the 1958 Birth Cohort (n = 1457; 1849 Y-DNA SNPs), and studied the robust associations between 32 SNPs and body mass index (BMI), including SNPs in or near Fat Mass and Obesity-associated protein (FTO) which yield the strongest effects. Overall, no association was replicated in both cohorts when Y-DNA haplogroups were considered and this suggests that, for BMI at least, there is little evidence of differences in phenotype or SNP association by Y-DNA structure. Further studies using other traits, phenome-wide association studies (PheWAS), other haplogroups and/or autosomal SNPs are required to test the generalisability and utility of this approach.
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