Dataset Information

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.

SUBMITTER: Anwar MY

PROVIDER: S-EPMC9464371 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Anwar Mohammad Yaser MY Baldassari Antoine R AR Polikowsky Hannah G HG Sitlani Colleen M CM Highland Heather M HM Chami Nathalie N Chen Hung-Hsin HH Graff Mariaelisa M Howard Annie Green AG Jung Su Yon SY Petty Lauren E LE Wang Zhe Z Zhu Wanying W Buyske Steven S Cheng Iona I Kaplan Robert R Kooperberg Charles C Loos Ruth J F RJF Peters Ulrike U McCormick Joseph B JB Fisher-Hoch Susan P SP Avery Christy L CL Taylor Kira C KC Below Jennifer E JE North Kari E KE

BMC medical genomics 20220910 1

<h4>Background</h4>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.<h4>Methods</ ...[more]

PMID: 36088317

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Project description:BackgroundHispanic/Latino (HL) populations bear a disproportionately high burden of type 2 diabetes (T2D). The ability to predict T2D genetic risk using polygenic risk scores (PRS) offers great promise for improved screening and prevention. However, there are a number of complications related to the accurate inference of genetic risk across HL populations with distinct ancestry profiles. We investigated how ancestry affects the inference of T2D genetic risk using PRS in diverse HL populations from Colombia and the United States (US). In Colombia, we compared T2D genetic risk for the Mestizo population of Antioquia to the Afro-Colombian population of Chocó, and in the US, we compared European-American versus Mexican-American populations.MethodsWhole genome sequences and genotypes from the 1000 Genomes Project and the ChocoGen Research Project were used for genetic ancestry inference and for T2D polygenic risk score (PRS) calculation. Continental ancestry fractions for HL genomes were inferred via comparison with African, European, and Native American reference genomes, and PRS were calculated using T2D risk variants taken from multiple genome-wide association studies (GWAS) conducted on cohorts with diverse ancestries. A correction for ancestry bias in T2D risk inference based on the frequencies of ancestral versus derived alleles was developed and applied to PRS calculations in the HL populations studied here.ResultsT2D genetic risk in Colombian and US HL populations is positively correlated with African and Native American ancestry and negatively correlated with European ancestry. The Afro-Colombian population of Chocó has higher predicted T2D risk than Antioquia, and the Mexican-American population has higher predicted risk than the European-American population. The inferred relative risk of T2D is robust to differences in the ancestry of the GWAS cohorts used for variant discovery. For trans-ethnic GWAS, population-specific variants and variants with same direction effects across populations yield consistent results. Nevertheless, the control for bias in T2D risk prediction confirms that explicit consideration of genetic ancestry can yield more reliable cross-population genetic risk inferences.ConclusionsT2D associations that replicate across populations provide for more reliable risk inference, and modeling population-specific frequencies of ancestral and derived risk alleles can help control for biases in PRS estimation.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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