Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
Lipids Health Dis. 2012 Nov 14;11:155. doi: 10.1186/1476-511X-11-155.
Genome wide association studies (GWAS), mostly in Europeans have identified several common variants as associated with key lipid traits. Replication of these genetic effects in South Asian populations is important since it would suggest wider relevance for these findings. Given the rising prevalence of metabolic disorders and heart disease in the Indian sub-continent, these studies could be of future clinical relevance.
We studied seven common variants associated with a variety of lipid traits in previous GWASs. The study sample comprised of 3178 sib-pairs recruited as participants for the Indian Migration Study (IMS). Associations with various lipid parameters and quantitative traits were analyzed using the Fulker genetic association model.
We replicated five of the 7 main effect associations with p-values ranging from 0.03 to 1.97x10(-7). We identified particularly strong association signals at rs662799 in APOA5 (beta=0.18 s.d, p=1.97 x 10(-7)), rs10503669 in LPL (beta =-0.18 s.d, p=1.0 x 10(-4)) and rs780094 in GCKR (beta=0.11 s.d, p=0.001) loci in relation to triglycerides. In addition, the GCKR variant was also associated with total cholesterol (beta=0.11 s.d, p=3.9x10(-4)). We also replicated the association of rs562338 in APOB (p=0.03) and rs4775041 in LIPC (p=0.007) with LDL-cholesterol and HDL-cholesterol respectively.
We report associations of five loci with various lipid traits with the effect size consistent with the same reported in Europeans. These results indicate an overlap of genetic effects pertaining to lipid traits across the European and Indian populations.
全基因组关联研究(GWAS)主要在欧洲人群中发现了几个与关键脂质特征相关的常见变异。在南亚人群中复制这些遗传效应非常重要,因为这表明这些发现具有更广泛的相关性。鉴于代谢紊乱和心脏病在印度次大陆的发病率不断上升,这些研究可能具有未来的临床意义。
我们研究了之前 GWAS 中与各种脂质特征相关的 7 个常见变异。研究样本包括作为印度移民研究(IMS)参与者招募的 3178 对同胞。使用 Fulker 遗传关联模型分析了与各种脂质参数和数量性状的关联。
我们复制了 7 个主要效应关联中的 5 个,p 值范围为 0.03 至 1.97x10(-7)。我们在 APOA5 中的 rs662799(beta=0.18 s.d,p=1.97 x 10(-7))、LPL 中的 rs10503669(beta=-0.18 s.d,p=1.0 x 10(-4))和 GCKR 中的 rs780094 位点发现了特别强的关联信号,与甘油三酯有关。此外,GCKR 变体也与总胆固醇相关(beta=0.11 s.d,p=0.001)。我们还复制了 APOB 中的 rs562338(p=0.03)和 LIPC 中的 rs4775041(p=0.007)与 LDL-胆固醇和 HDL-胆固醇的关联。
我们报告了五个与各种脂质特征相关的基因座与在欧洲人群中报道的相同的效应大小的关联。这些结果表明,欧洲和印度人群中脂质特征的遗传效应存在重叠。