习惯性喝咖啡的全基因组关联研究揭示了日本人群中 12q24 位点的遗传效应存在性别差异。
GWAS of habitual coffee consumption reveals a sex difference in the genetic effect of the 12q24 locus in the Japanese population.
机构信息
Health Nutrition, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Genequest Inc., 5-29-11 Siba, Minato-ku, Tokyo, 108-0014, Japan.
出版信息
BMC Genet. 2019 Jul 26;20(1):61. doi: 10.1186/s12863-019-0763-7.
BACKGROUND
Studies on genetic effects of coffee consumption are scarce for Asian populations. We conducted a genome-wide association study (GWAS) of habitual coffee consumption in Japan using a self-reporting online survey.
RESULTS
Candidate genetic loci associated with habitual coffee consumption were searched within a discovery cohort (N = 6,264) and confirmed in a replication cohort (N = 5,975). Two loci achieved genome-wide significance (P < 5 × 10) in a meta-analysis of the discovery and replication cohorts: an Asian population-specific 12q24 (rs79105258; P = 9.5 × 10), which harbors CUX2, and 7p21 (rs10252701; P = 1.0 × 10), in the upstream region of the aryl hydrocarbon receptor (AHR) gene, involved in caffeine metabolism. Subgroup analysis revealed a stronger genetic effect of the 12q24 locus in males (P for interaction = 8.2 × 10). Further, rs79105258 at the 12q24 locus exerted pleiotropic effects on body mass index (P = 3.5 × 10) and serum triglyceride levels (P = 8.7 × 10).
CONCLUSIONS
Our results consolidate the association of habitual coffee consumption with the 12q24 and 7p21 loci. The different effects of the 12q24 locus between males and females are a novel finding that improves our understanding of genetic influences on habitual coffee consumption.
背景
针对亚洲人群的咖啡摄入遗传效应研究较为匮乏。我们通过一份在线的自我报告式问卷调查，在日本人群中开展了一项针对习惯性咖啡摄入的全基因组关联研究（GWAS）。
结果
在一项包含 6264 例个体的发现队列中对习惯性咖啡摄入的候选遗传位点进行了搜索，并在一项包含 5975 例个体的验证队列中对其进行了验证。在发现队列和验证队列的汇总分析中，有两个位点达到了全基因组关联显著性（P < 5×10）：一个位于 12q24 的亚洲人群特异性位点（rs79105258；P = 9.5×10），该位点包含 CUX2 基因；另一个位于 7p21 的位点（rs10252701；P = 1.0×10），位于芳香烃受体（AHR）基因的上游区域，该基因参与咖啡因代谢。亚组分析显示，12q24 位点的遗传效应在男性中更强（P 交互作用= 8.2×10）。此外，12q24 位点的 rs79105258 对体重指数（P = 3.5×10）和血清甘油三酯水平（P = 8.7×10）具有显著的多效性影响。
结论
我们的研究结果证实了习惯性咖啡摄入与 12q24 和 7p21 位点的相关性。12q24 位点在男性和女性中的不同效应是一个新的发现，它提高了我们对遗传因素对习惯性咖啡摄入影响的理解。
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