@article{52f37d0727ad4389933eb0e6240a9552,
title = "Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations",
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.",
keywords = "Genetic pleiotropy, Hispanic Americans, Inflammation, Obesity",
author = "Anwar, {Mohammad Yaser} and Baldassari, {Antoine R.} and Polikowsky, {Hannah G.} and Sitlani, {Colleen M.} and Highland, {Heather M.} and Nathalie Chami and Chen, {Hung Hsin} and Mariaelisa Graff and Howard, {Annie Green} and Jung, {Su Yon} and Petty, {Lauren E.} and Zhe Wang and Wanying Zhu and Steven Buyske and Iona Cheng and Robert Kaplan and Charles Kooperberg and Loos, {Ruth J.F.} and Ulrike Peters and McCormick, {Joseph B.} and Fisher-Hoch, {Susan P.} and Avery, {Christy L.} and Taylor, {Kira C.} and Below, {Jennifer E.} and North, {Kari E.}",
note = "Funding Information: The PAGE Study is funded by the National Human Genome Research Institute with co-funding from the National Institute on Minority Health and Health Disparities. Assistance with data management, data integration, data dissemination, genotype imputation, ancestry deconvolution, population genetics, analysis pipelines and general study coordination was provided by the PAGE Coordinating Center (NI-HU01HG007419). Genotyping services were provided by the Center for Inherited Disease Research, which is fully funded through a federal contract from the National Institutes of Health (NIH) to The Johns Hopkins University, contract number HHSN268201200008I. Genotype data quality control and quality assurance services were provided by the Genetic Analysis Center in the Biostatistics Department of the University of Washington, through support provided by the Center for Inherited Disease Research contract. PAGE was also funded by grants R56HG010297 and R01HG010297. PAGE data and materials included in this report were funded through the following studies and organizations: The Mount Sinai BioMe Biobank is supported by The Andrea and Charles Bronfman Philanthropies. The MEC characterization of epidemiological architecture is funded through the NHGRI PAGE program (U01HG004802 and its NHGRI ARRA supplement). The MEC study is funded by the National Cancer Institute (R37CA54281, R01CA63, P01CA33619, U01CA136792 and U01CA98758). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Services through contracts 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004 and 75N92021D00005. The HCHS/SOL is a collaborative study supported by contracts from the National Heart, Lung and Blood Institute (NHLBI) to the University of North Carolina (HHSN268201300001I / N01-HC-65233), University of Miami (HHSN268201300004I / N01-HC-65234), Albert Einstein College of Medicine (HHSN268201300002I / N01-HC 65235), University of Illinois at Chicago (HHSN268201300003I / N01-HC-65236 Northwestern University), and San Diego State University (HHSN268201300005I / N01-HC-65237). The following Institutes/Centres/Offices have contributed to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities; National Institute on Deafness and Other Communication Disorders; National Institute of Dental and Craniofacial Research; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Neurological Disorders and Stroke; and NIH Institution-Office of Dietary Supplements. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03. The CCHC is supported by MD000170 P20 funded from the National Center on Minority Health and Health Disparities (NCMHD), the University of Texas Houston Health Sciences Center, Center for Clinical and Translational Science CCTS-CTSA award UL1 TR00371 from NCATS. MYA is funded by NIDDK grant # 3R01DK122503 – 02W1. HMH is funded by NHLBI training grant T32 HL129982, ADA Grant #1-19-PDF-045, and R01HL142825. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1186/s12920-022-01352-3",
language = "English (US)",
volume = "15",
journal = "BMC Medical Genomics",
issn = "1755-8794",
publisher = "BioMed Central",
number = "1",
}
