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全基因组荟萃分析揭示了韩国人群血清尿酸水平与多个遗传位点相关:韩国生物银行数据分析。

Genome-wide meta-analysis revealed several genetic loci associated with serum uric acid levels in Korean population: an analysis of Korea Biobank data.

机构信息

Department of Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea.

Division of Rheumatology, Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea.

出版信息

J Hum Genet. 2022 Apr;67(4):231-237. doi: 10.1038/s10038-021-00991-1. Epub 2021 Nov 1.

Abstract

The serum uric acid (SUA) level is an important determinant of gout, hypertension, metabolic syndrome, and cardiovascular disease. Although previous genome-wide studies have identified multiple genetic variants associated with SUA, most genetic analyses have focused on individuals with European ancestry; thus, understanding of the genetic architecture of SUA is currently limited for Asian populations. We conducted a genome-wide meta-analysis based on Korea Biobank data consistent with three cohorts; namely, the Korean Genome and Epidemiology Study (KoGES) Ansan and Ansung, KoGES Health Examinee, and KoGES Cardiovascular Disease Association studies. In total, 60,585 participants aged ≥40 years were included in the analysis of the three cohorts. We used logistic regression analyses to perform genome-wide association study (GWAS) adjustments for confounding variables. Subsequently, a meta-analysis was conducted by combining the analyses of the three GWASs. We identified 8,105 variants at 22 genetic loci with a P value < 5 × 10. Among these, six novel genetic loci associated with SUA in the Korean population were identified (rs4715517 in HCRTR2, rs145099458 in 3.2 kb 3' of MLXIPL, rs1137642 in B4GALT1, rs659107 in LOC105378410, rs7919329 in LOC107984274, and rs2240751 in MFSD12). Our meta-analysis provides insights into the genetic architecture of SUA in the Korean population. Further studies are warranted to replicate the study results and elucidate the specific role of these variants in SUA homeostasis.

摘要

血清尿酸 (SUA) 水平是痛风、高血压、代谢综合征和心血管疾病的重要决定因素。虽然之前的全基因组研究已经确定了多个与 SUA 相关的遗传变异,但大多数遗传分析都集中在欧洲血统的个体上;因此,目前对亚洲人群 SUA 的遗传结构的了解是有限的。我们基于韩国生物银行数据进行了一项全基因组荟萃分析,该数据与三个队列一致;即韩国基因组和流行病学研究 (KoGES) 安山和安城、KoGES 健康体检者和 KoGES 心血管疾病协会研究。共有 60585 名年龄≥40 岁的参与者纳入了三个队列的分析。我们使用逻辑回归分析对混杂变量进行全基因组关联研究 (GWAS) 调整。随后,通过合并三个 GWAS 的分析进行荟萃分析。我们在 22 个遗传位点确定了 8105 个具有 P 值<5×10 的变异。其中,在韩国人群中发现了 6 个与 SUA 相关的新遗传位点(rs4715517 在 HCRTR2 中、rs145099458 在 MLXIPL 的 3.2kb 3'中、rs1137642 在 B4GALT1 中、rs659107 在 LOC105378410 中、rs7919329 在 LOC107984274 中、rs2240751 在 MFSD12 中)。我们的荟萃分析提供了对韩国人群 SUA 遗传结构的见解。需要进一步的研究来复制研究结果,并阐明这些变异在 SUA 稳态中的具体作用。

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