Department of Medical Sciences, Molecular Epidemiology, Uppsala University, EpiHubben, MTC-huset, 751 85, Uppsala, Sweden.
Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Diabetologia. 2018 Oct;61(10):2174-2179. doi: 10.1007/s00125-018-4686-z. Epub 2018 Jul 12.
AIMS/HYPOTHESIS: Coronary artery disease (CAD) is a common complication among individuals with diabetes. A better understanding of the genetic background of CAD in this population has the potential to suggest novel molecular targets for screening, risk assessment and drug development.
We performed a genome-wide association study of CAD in 15,666 unrelated individuals (3,968 CAD cases and 11,698 controls) of white British ancestry with diabetes at inclusion in the UK Biobank study. Our results were compared with results from participants without diabetes.
We found genome-wide significant evidence for association with CAD at the previously well-established LPA locus (lead variant: rs74617384; OR 1.38 [95% CI 1.26, 1.51], p = 3.2 × 10) and at 9p21 (lead variant: rs10811652; OR 1.19 [95% CI 1.13, 1.26], p = 6.0 × 10). Moreover, other variants previously associated with CAD showed similar effects in the participants with and without diabetes, indicating that the genetic architecture of CAD is largely the same.
CONCLUSIONS/INTERPRETATION: Our results indicate large similarities between the genetic architecture of CAD in participants with and without diabetes. Larger studies are needed to establish whether there are important diabetes-specific CAD loci.
目的/假设:冠心病(CAD)是糖尿病患者的常见并发症。更好地了解该人群中 CAD 的遗传背景有可能为筛查、风险评估和药物开发提供新的分子靶点。
我们对英国生物库研究中纳入的 15666 名无血缘关系的白种英国人(3968 例 CAD 病例和 11698 例对照)进行了 CAD 的全基因组关联研究。我们的结果与无糖尿病的参与者的结果进行了比较。
我们发现先前在 LPA 基因座(先导变异:rs74617384;OR 1.38[95%CI 1.26,1.51],p=3.2×10)和 9p21 处(先导变异:rs10811652;OR 1.19[95%CI 1.13,1.26],p=6.0×10)与 CAD 有全基因组显著关联的证据。此外,先前与 CAD 相关的其他变异在有糖尿病和无糖尿病的参与者中也表现出类似的效果,表明 CAD 的遗传结构基本相同。
结论/解释:我们的结果表明,有糖尿病和无糖尿病的 CAD 遗传结构之间有很大的相似性。需要更大的研究来确定是否存在重要的糖尿病特异性 CAD 基因座。