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

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. McCormickSusan P. Fisher-Hoch, Christy L. Avery, Kira C. Taylor, Jennifer E. Below, Kari E. North

Epidemiology & Population Health

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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.

Original language	English (US)
Article number	192
Journal	BMC Medical Genomics
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s12920-022-01352-3
State	Published - Dec 2022

Keywords

Genetic pleiotropy
Hispanic Americans
Inflammation
Obesity

ASJC Scopus subject areas

Genetics
Genetics(clinical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12920-022-01352-3

Cite this

Anwar, M. Y., Baldassari, A. R., Polikowsky, H. G., Sitlani, C. M., Highland, H. M., Chami, N., Chen, H. H., Graff, M., Howard, A. G., Jung, S. Y., Petty, L. E., Wang, Z., Zhu, W., Buyske, S., Cheng, I., Kaplan, R., Kooperberg, C., Loos, R. J. F., Peters, U., ... North, K. E. (2022). Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations. BMC Medical Genomics, 15(1), Article 192. https://doi.org/10.1186/s12920-022-01352-3

Anwar, MY, Baldassari, AR, Polikowsky, HG, Sitlani, CM, Highland, HM, Chami, N, Chen, HH, Graff, M, Howard, AG, Jung, SY, Petty, LE, Wang, Z, Zhu, W, Buyske, S, Cheng, I, Kaplan, R, Kooperberg, C, Loos, RJF, Peters, U, McCormick, JB, Fisher-Hoch, SP, Avery, CL, Taylor, KC, Below, JE & North, KE 2022, 'Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations', BMC Medical Genomics, vol. 15, no. 1, 192. https://doi.org/10.1186/s12920-022-01352-3

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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.}",

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year = "2022",

month = dec,

doi = "10.1186/s12920-022-01352-3",

language = "English (US)",

volume = "15",

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T1 - Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations

AU - Anwar, Mohammad Yaser

AU - Baldassari, Antoine R.

AU - Polikowsky, Hannah G.

AU - Sitlani, Colleen M.

AU - Highland, Heather M.

AU - Chami, Nathalie

AU - Chen, Hung Hsin

AU - Graff, Mariaelisa

AU - Howard, Annie Green

AU - Jung, Su Yon

AU - Petty, Lauren E.

AU - Wang, Zhe

AU - Zhu, Wanying

AU - Buyske, Steven

AU - Cheng, Iona

AU - Kaplan, Robert

AU - Kooperberg, Charles

AU - Loos, Ruth J.F.

AU - Peters, Ulrike

AU - McCormick, Joseph B.

AU - Fisher-Hoch, Susan P.

AU - Avery, Christy L.

AU - Taylor, Kira C.

AU - Below, Jennifer E.

AU - North, Kari E.

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

KW - Genetic pleiotropy

KW - Hispanic Americans

KW - Inflammation

KW - Obesity

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VL - 15

JO - BMC Medical Genomics

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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