Department of Epidemiology, University of North Carolina at Chapel Hill, 123 West Franklin Street, CVD Genetic Epidemiology Lab, Fl #4, Room A7, Chapel Hill, NC, 27599, USA.
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
BMC Med Genomics. 2022 Sep 10;15(1):192. doi: 10.1186/s12920-022-01352-3.
Concurrent variation in adiposity and inflammation suggests potential shared functional pathways and pleiotropic disease underpinning. Yet, exploration of pleiotropy in the context of adiposity-inflammation has been scarce, and none has included self-identified Hispanic/Latino populations. Given the high level of ancestral diversity in Hispanic American population, genetic studies may reveal variants that are infrequent/monomorphic in more homogeneous populations.
Using multi-trait Adaptive Sum of Powered Score (aSPU) method, we examined individual and shared genetic effects underlying inflammatory (CRP) and adiposity-related traits (Body Mass Index [BMI]), and central adiposity (Waist to Hip Ratio [WHR]) in HLA participating in the Population Architecture Using Genomics and Epidemiology (PAGE) cohort (N = 35,871) with replication of effects in the Cameron County Hispanic Cohort (CCHC) which consists of Mexican American individuals.
Of the > 16 million SNPs tested, variants representing 7 independent loci were found to illustrate significant association with multiple traits. Two out of 7 variants were replicated at statistically significant level in multi-trait analyses in CCHC. The lead variant on APOE (rs439401) and rs11208712 were found to harbor multi-trait associations with adiposity and inflammation.
Results from this study demonstrate the importance of considering pleiotropy for improving our understanding of the etiology of the various metabolic pathways that regulate cardiovascular disease development.
肥胖和炎症的同时变化表明存在潜在的共同功能途径和多效性疾病基础。然而，在肥胖-炎症的背景下探索多效性的研究很少，而且都没有包括自我认同的西班牙裔/拉丁裔人群。鉴于西班牙裔美国人种的祖先多样性程度很高，遗传研究可能会揭示在更同质的人群中罕见/单态的变异体。
我们使用多性状自适应加和得分（aSPU）方法，研究了炎症（CRP）和肥胖相关性状（体重指数 [BMI]）以及中央肥胖（腰臀比 [WHR]）在 HLA 中的个体和共同遗传效应，该研究参与了人口基因组学和流行病学（PAGE）队列（N = 35871），并在卡梅伦县西班牙裔队列（CCHC）中对效应进行了复制，CCHC 由墨西哥裔美国人组成。
在测试的超过 1600 万个 SNP 中，有 7 个独立的位点代表的变体被发现与多种性状显著相关。在 CCHC 的多性状分析中，有 2 个变体在统计学上达到了显著水平的复制。APOE 上的主要变体（rs439401）和 rs11208712 被发现与肥胖和炎症具有多性状关联。
这项研究的结果表明，考虑多效性对于提高我们对调节心血管疾病发展的各种代谢途径的病因的理解非常重要。
