PDF(Pubmed)
Abstract：
Genome-wide association studies (GWAS) have identified many genetic variants associated with alcohol consumption in Europeans and East Asians, as well as other populations. However, the genetic homogeneity and heterogeneity between these populations have not been thoroughly investigated, despite evidence of varying effect sizes of variants between ethnicities and the presence of population-specific strong signals of selection on loci associated with alcohol consumption. In order to better understand the relationship between Europeans and East Asians in the genetic architecture of alcohol consumption, we compared their heritability and evaluated their genetic correlation using GWAS results from UK Biobank (UKB) and Biobank Japan (BBJ). We found that these two populations have low genetic correlation due to the large difference on chromosome 12. After excluding this chromosome, the genetic correlation was moderately high ([Formula: see text] = 0.544, p = 1.12e-4) and 44.31% of the genome-wide causal variants were inferred to be shared between Europeans and East Asians. Given those observations, we conducted a meta-analysis on UKB and BBJ and identified new signals, including the CADM2 gene on chromosome 3, which has been associated with various behavioral and metabolic traits. Overall, our findings suggest that the genetic architecture of alcohol consumption is largely shared between Europeans and East Asians, but there are exceptions such as the enrichment of heritability on chromosome 12 in East Asians.
摘要：
全基因组关联研究（GWAS）已经确定了许多与欧洲人和东亚人饮酒相关的遗传变异，以及其他人群。然而,这些种群之间的遗传同质性和异质性尚未得到彻底调查，尽管有证据表明，不同种族之间变异的影响大小不同，并且在与饮酒相关的基因座上存在特定于人群的强选择信号。为了更好地了解欧洲人和东亚人在饮酒的遗传结构中的关系，我们比较了它们的遗传力,并使用英国生物库(UKB)和日本生物库(BBJ)的GWAS结果评估了它们的遗传相关性.我们发现，由于12号染色体上的差异很大，这两个种群的遗传相关性较低。排除这个染色体后,遗传相关性中等高([公式:见正文]=0.544,p=1.12e-4),推断有44.31%的全基因组因果变异在欧洲人和东亚人之间共有.鉴于这些观察,我们对UKB和BBJ进行了荟萃分析，并确定了新的信号，包括3号染色体上的CADM2基因，该基因与各种行为和代谢性状有关。总的来说,我们的研究结果表明，饮酒的基因结构在欧洲人和东亚人之间有很大的共同点，但是也有例外，例如东亚人在12号染色体上的遗传力丰富。
