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.
BMC Genet. 2019 Jul 26;20(1):61. doi: 10.1186/s12863-019-0763-7.
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.
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).
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.
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）。
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。
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。
