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- 8) in a meta-analysis of the discovery and replication cohorts: an Asian population-specific 12q24 (rs79105258; P = 9.5 × 10- 15), which harbors CUX2, and 7p21 (rs10252701; P = 1.0 × 10- 14), 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- 5). Further, rs79105258 at the 12q24 locus exerted pleiotropic effects on body mass index (P = 3.5 × 10- 4) and serum triglyceride levels (P = 8.7 × 10- 3). 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.

中文翻译：

---

GWAS的习惯性咖啡消费揭示了日本人口中12q24基因座的遗传效应存在性别差异。

背景技术关于咖啡消费的遗传效应的研究对于亚洲人群而言是很少的。我们使用自我报告在线调查进行了日本惯常咖啡消费的全基因组关联研究（GWAS）。结果在发现队列（N = 6,264）中搜索了与习惯性咖啡消费相关的候选遗传基因座，并在复制队列（N = 5,975）中进行了确认。在发现和复制队列的荟萃分析中，两个基因座达到了全基因组意义（P <5×10-8）：亚洲特定人群12q24（rs79105258; P = 9.5×10-15），其中带有CUX2，和7p21（rs10252701; P = 1.0×10-14），在芳烃受体（AHR）基因的上游区域，参与咖啡因的代谢。亚组分析显示，男性12q24基因座具有更强的遗传效应（相互作用的P = 8。2×10-5）。此外，位于12q24位点的rs79105258对体重指数（P = 3.5×10-4）和血清甘油三酯水平（P = 8.7×10-3）表现出多效性作用。结论我们的结果巩固了习惯咖啡消费与12q24和7p21位点的关联。雄性和雌性之间12q24基因座的不同影响是一个新颖的发现，可增进我们对习惯性咖啡消费的遗传影响的理解。