Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations

• DOI: 10.1186/s12920-022-01352-3
• Publication Date: 2022-09-10T14:02:24Z
• Authors: Mohammad Yaser Anwar; Antoine R. Baldas...; Hannah G. Polikowsky; Colleen M. Sitlani; Heather M. Highland; Nathalie Chami; Hung-Hsin Chen; Mariaelisa Graff; Annie Green Howard; Su Yon Jung; Lauren E. Petty; Zhe Wang; Wanying Zhu; Steven Buyske; Iona Cheng; Robert Kaplan; Charles Kooperberg; Ruth J. F. Loos; Ulrike Peters; Joseph B. McCormick; Susan P. Fisher-Hoch; Christy L. Avery; Kira C. Taylor; Jennifer E. Below; Kari E. North
• Keywords: Genetics & Heredity; Inflammation; Research; Human Genome; Oncology and Carcinogenesis; 610; Genetic Pleiotropy; Hispanic or Latino; Biological Sciences; Medical Biochemistry and Metabolomics; QH426-470; RC31-1245; 3. Good health; Clinical Research; 616; Genetics; 2.1 Biological and endogenous factors; Medical biochemistry and metabolomics; Humans; Genetic pleiotropy; Obesity; Aetiology; Hispanic Americans; Internal medicine; Adiposity

Abstract Background 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.

Methods 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.

Results 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.

Conclusions 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.