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Extended genetic effects of ADH cluster genes on the risk of alcohol dependence: From GWAS to replication

机译:ADH簇基因对酒精依赖风险的扩展遗传影响:从GWAS到复制

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Alcohol dependence (AD) is a multifactorial and polygenic disorder involving complex gene-to-gene and gene-to-environment interactions. Several genome-wide association studies have reported numerous risk factors for AD, but replication results following these studies have been controversial. To identify new candidate genes, the present study used GWAS and replication studies in a Korean cohort with AD. Genome-wide association analysis revealed that two chromosome regions on Chr. 4q22-q23 (ADH gene cluster, including ADH5, ADH4, ADH6, ADH1A, ADH1B, and ADH7) and Chr. 12q24 (ALDH2) showed multiple association signals for the risk of AD. To investigate detailed genetic effects of these ADH genes on AD, a follow-up study of the ADH gene cluster on 4q22-q23 was performed. A total of 90 SNPs, including ADH1B rs1229984 (H47R), were genotyped in an additional 975 Korean subjects. In case-control analysis, ADH1B rs1229984 (H47R) showed the most significant association with the risk of AD (p = 2.63 × 10-21, OR = 2.35). Moreover, subsequent conditional analyses revealed that all positive associations of other ADH genes in the cluster disappeared, which suggested that ADH1B rs1229984 (H47R) might be the sole functional genetic marker across the ADH gene cluster. Our findings could provide additional information on the ADH gene cluster regarding the risk of AD, as well as a new and important insight into the genetic factors associated with AD.
机译:酒精依赖(AD)是一种多因素多基因疾病,涉及复杂的基因间相互作用和基因间环境相互作用。几项全基因组关联研究报告了许多AD危险因素,但这些研究后的复制结果引起争议。为了鉴定新的候选基因,本研究在韩国AD人群中使用了GWAS和复制研究。全基因组关联分析显示,Chr上有两个染色体区域。 4q22-q23(ADH基因簇,包括ADH5,ADH4,ADH6,ADH1A,ADH1B和ADH7)和Chr。 12q24(ALDH2)显示出多种与AD风险相关的信号。为了研究这些ADH基因对AD的详细遗传效应,对ADH基因簇在4q22-q23上的后续研究。在另外975名韩国受试者中对包括ADH1B rs1229984(H47R)在内的总共90个SNP进行了基因分型。在病例对照分析中,ADH1B rs1229984(H47R)显示与AD风险之间的关联最为显着(p = 2.63×10-21,OR = 2.35)。此外,随后的条件分析表明,簇中其他ADH基因的所有正相关性都消失了,这表明ADH1B rs1229984(H47R)可能是整个ADH基因簇的唯一功能遗传标记。我们的发现可能提供有关AD风险的ADH基因簇的其他信息,以及对与AD相关的遗传因素的新的重要见解。

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