Department of Statistics, Seoul National University, Seoul, 08826, Republic of Korea.
Daegu Institution, National Forensic Service, 33-14, Hogukro, Waegwon-eup, Chilgok-gun, Gyeomgsamgbuk-do, Republic of Korea.
Sci Rep. 2018 Apr 9;8(1):5701. doi: 10.1038/s41598-018-23074-2.
To identify novel loci for susceptibility to MetS, we conducted genome-wide association and exome wide association studies consisting of a discovery stage cohort (KARE, 1946 cases and 6427 controls), and a replication stage cohort (HEXA, 430 cases and 3,264 controls). For finding genetic variants for MetS, with its components, we performed multivariate analysis for common and rare associations, using a standard logistic regression analysis for MetS. From the discovery and replication GWA studies, we confirmed 21 genome-wide signals significantly associated with MetS. Of these 21, four were previously unreported to associate with any MetS components: rs765547 near LPL; rs3782889 in MYL2; and rs11065756 and rs10849915 in CCDC63. Using exome chip variants, gene-based analysis of rare variants revealed three genes, CETP, SH2B1, and ZFP2, in the discovery stage, among which only CETP was confirmed in the replication stage. Finally, CETP D442G (rs2303790) associated, as a less common variant, with decreased risk of MetS. In conclusion, we discovered a total of five new MetS-associated loci, and their overlap with other disease-related components, suggest roles in the various etiologies of MetS, and its possible preventive strategies.
为了确定代谢综合征易感性的新基因座，我们进行了全基因组关联和外显子组关联研究，包括一个发现阶段队列（KARE，1946 例病例和 6427 例对照）和一个复制阶段队列（HEXA，430 例病例和 3264 例对照）。为了寻找代谢综合征及其成分的遗传变异，我们使用标准的逻辑回归分析对常见和罕见关联进行了多变量分析。从发现和复制的 GWAS 研究中，我们确认了与代谢综合征显著相关的 21 个全基因组信号。在这 21 个信号中，有 4 个以前没有报道与任何代谢综合征成分相关：LPL 附近的 rs765547；MYL2 中的 rs3782889；以及 CCDC63 中的 rs11065756 和 rs10849915。使用外显子芯片变体，对罕见变体进行基于基因的分析，在发现阶段发现了三个基因，CETP、SH2B1 和 ZFP2，其中只有 CETP 在复制阶段得到了证实。最后，CETP D442G(rs2303790)作为一种较少见的变体，与代谢综合征风险降低相关。总之，我们总共发现了 5 个新的代谢综合征相关基因座，它们与其他与疾病相关的成分重叠，提示它们在代谢综合征的各种病因中的作用，以及可能的预防策略。
