Kim Yun Kyoung, Hwang Mi Yeong, Kim Young Jin, Moon Sanghoon, Han Sohee, Kim Bong-Jo
Division of Structural and Functional Genomics, Center for Genome Sciences, National Institute of Health, Centers for Disease Control and Prevention, Cheongju-si, Chungcheongbuk-do, 28159, South Korea.
Cardiovasc Diabetol. 2016 Feb 1;15:20. doi: 10.1186/s12933-016-0337-1.
The genetic contribution to complex diseases or traits, including cardio-metabolic traits, has been elucidated recently by large-scale genome-wide association studies. These genome-wide association studies have indicated that most pleiotropic loci contain genes associated with lipids. Clinically, lipid related abnormalities are strongly associated with other diseases such as type 2 diabetes, coronary artery disease and hypertension. The aim of this study was to evaluate the shared genetic background of lipids and other cardio-metabolic traits.
We conducted meta-analyses of the association between 157 published lipid-associated loci and 10 cardio-metabolic traits in 14,028 Korean individuals genotyped using the Exome chip (Illumina HumanExome BeadChip). We also examined whether the pleiotropic effects of such loci constituted independent (i.e., biological) pleiotropy or mediated pleiotropy in these metabolic pathways.
Eighteen lipid-associated loci were significantly associated with one of six cardio-metabolic traits after correction for multiple testing (P < 3.70 × 10(-4)). Region 12q24.12 had pleiotropic effects on fasting plasma glucose, blood pressure and obesity-related traits (body mass index and waist-hip ratio) independent of its effects on the lipid profile. Lipid risk scores, calculated according to whether or not subjects carried the risk allele for lipid traits, were significantly associated with fasting plasma glucose, blood pressure and obesity-related traits.
The 12q24.12 region showed ethnic-specific genetic pleiotropy among cardio-metabolic traits in this study. Our findings may help to account for molecular mechanisms based on shared genetic background underlying not only dyslipidemia, but also cardiovascular disease and type 2 diabetes.
近期大规模全基因组关联研究已经阐明了基因对包括心血管代谢性状在内的复杂疾病或性状的贡献。这些全基因组关联研究表明，大多数多效性位点包含与脂质相关的基因。临床上，脂质相关异常与其他疾病如2型糖尿病、冠状动脉疾病和高血压密切相关。本研究的目的是评估脂质与其他心血管代谢性状的共同遗传背景。
我们对157个已发表的脂质相关位点与14028名使用外显子芯片（Illumina HumanExome BeadChip）进行基因分型的韩国个体的10种心血管代谢性状之间的关联进行了荟萃分析。我们还研究了这些位点的多效性效应在这些代谢途径中是构成独立（即生物学）多效性还是介导多效性。
在进行多重检验校正后，18个脂质相关位点与六种心血管代谢性状之一显著相关（P < 3.70×10⁻⁴）。12q24.12区域对空腹血糖、血压和肥胖相关性状（体重指数和腰臀比）具有多效性效应，独立于其对脂质谱的影响。根据受试者是否携带脂质性状的风险等位基因计算的脂质风险评分与空腹血糖、血压和肥胖相关性状显著相关。
在本研究中，12q24.12区域在心血管代谢性状中表现出种族特异性的遗传多效性。我们的发现可能有助于解释不仅基于血脂异常，而且基于心血管疾病和2型糖尿病潜在共同遗传背景的分子机制。
