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

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 population...

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Detalles Bibliográficos
Autores principales: Anwar, Mohammad Yaser, Baldassari, Antoine R., Polikowsky, Hannah G., Sitlani, Colleen M., Highland, Heather M., Chami, Nathalie, Chen, Hung-Hsin, Graff, Mariaelisa, Howard, Annie Green, Jung, Su Yon, Petty, Lauren E., Wang, Zhe, Zhu, Wanying, Buyske, Steven, Cheng, Iona, Kaplan, Robert, Kooperberg, Charles, Loos, Ruth J. F., Peters, Ulrike, McCormick, Joseph B., Fisher-Hoch, Susan P., Avery, Christy L., Taylor, Kira C., Below, Jennifer E., North, Kari E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464371/
https://www.ncbi.nlm.nih.gov/pubmed/36088317
http://dx.doi.org/10.1186/s12920-022-01352-3
Descripción
Sumario: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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01352-3.