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

Mohammad Yaser Anwar; Antoine R Baldassari; 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

doi:10.1186/s12920-022-01352-3

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

BMC Med Genomics. 2022 Sep 10;15(1):192. doi: 10.1186/s12920-022-01352-3.

Authors

Mohammad Yaser Anwar¹, Antoine R Baldassari², Hannah G Polikowsky³, Colleen M Sitlani⁴, Heather M Highland², Nathalie Chami⁵, Hung-Hsin Chen³, Mariaelisa Graff², Annie Green Howard^{6

7}, Su Yon Jung^{8

9}, Lauren E Petty³, Zhe Wang⁵, Wanying Zhu³, Steven Buyske¹⁰, Iona Cheng¹¹, Robert Kaplan¹², Charles Kooperberg¹³, Ruth J F Loos⁵, Ulrike Peters¹³, Joseph B McCormick¹⁴, Susan P Fisher-Hoch¹⁴, Christy L Avery^{2

7}, Kira C Taylor¹⁵, Jennifer E Below³, Kari E North²

Affiliations

¹ 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. myaser@unc.edu.
² 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.
³ Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
⁴ Department of Medicine, University of Washington, Seattle, WA, 98195, USA.
⁵ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
⁷ Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27516, USA.
⁸ Translational Sciences Section, School of Nursing, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁹ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
¹⁰ Department of Statistics, Rutgers University, Piscataway, NJ, 08854, USA.
¹¹ Department of Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, 94115, USA.
¹² Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
¹³ Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
¹⁴ School of Public Health, University of Texas Health Science Center at Houston, Brownsville Regional Campus, Brownsville, TX, 78520, USA.
¹⁵ Department of Epidemiology and Population Health, University of Louisville School of Public Health and Information Sciences, Louisville, KT, 40202, USA.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adiposity* / genetics
Genetic Pleiotropy*
Hispanic or Latino / genetics
Humans
Inflammation / genetics
Obesity / genetics

Abstract

Publication types

MeSH terms

Grants and funding