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Meeks KAC, Bentley AR, Gouveia MH, et al. Genome-wide analyses of multiple obesity-related cytokines and hormones informs biology of cardiometabolic traits. Genome Med. 2021;13(1):156doi: 10.1186/s13073-021-00971-2.
Meeks, K. A. C., Bentley, A. R., Gouveia, M. H., Chen, G., Zhou, J., Lei, L., Adeyemo, A. A., Doumatey, A. P., & Rotimi, C. N. (2021). Genome-wide analyses of multiple obesity-related cytokines and hormones informs biology of cardiometabolic traits. Genome medicine, 13(1), 156. https://doi.org/10.1186/s13073-021-00971-2
Meeks, Karlijn A C, et al. "Genome-wide analyses of multiple obesity-related cytokines and hormones informs biology of cardiometabolic traits." Genome medicine vol. 13,1 (2021): 156. doi: https://doi.org/10.1186/s13073-021-00971-2
Meeks KAC, Bentley AR, Gouveia MH, Chen G, Zhou J, Lei L, Adeyemo AA, Doumatey AP, Rotimi CN. Genome-wide analyses of multiple obesity-related cytokines and hormones informs biology of cardiometabolic traits. Genome Med. 2021 Oct 07;13(1):156. doi: 10.1186/s13073-021-00971-2. PMID: 34620218; PMCID: PMC8499470.
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Genome Med. 2021 Oct 07;13(1):156. doi: 10.1186/s13073-021-00971-2.

Genome-wide analyses of multiple obesity-related cytokines and hormones informs biology of cardiometabolic traits.

Genome medicine

Karlijn A C Meeks, Amy R Bentley, Mateus H Gouveia, Guanjie Chen, Jie Zhou, Lin Lei, Adebowale A Adeyemo, Ayo P Doumatey, Charles N Rotimi

Affiliations

  1. Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive Bldg 12A rm 4047, Bethesda, MD, 20814, USA.
  2. Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive Bldg 12A rm 4047, Bethesda, MD, 20814, USA. [email protected].
  3. Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive Bldg 12A rm 4047, Bethesda, MD, 20814, USA. [email protected].

PMID: 34620218 PMCID: PMC8499470 DOI: 10.1186/s13073-021-00971-2

Abstract

BACKGROUND: A complex set of perturbations occur in cytokines and hormones in the etiopathogenesis of obesity and related cardiometabolic conditions such as type 2 diabetes (T2D). Evidence for the genetic regulation of these cytokines and hormones is limited, particularly in African-ancestry populations. In order to improve our understanding of the biology of cardiometabolic traits, we investigated the genetic architecture of a large panel of obesity- related cytokines and hormones among Africans with replication analyses in African Americans.

METHODS: We performed genome-wide association studies (GWAS) in 4432 continental Africans, enrolled from Ghana, Kenya, and Nigeria as part of the Africa America Diabetes Mellitus (AADM) study, for 13 obesity-related cytokines and hormones, including adipsin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), interleukin-1 receptor antagonist (IL1-RA), interleukin-6 (IL-6), interleukin-10 (IL-10), leptin, plasminogen activator inhibitor-1 (PAI-1), resistin, visfatin, insulin, glucagon, and ghrelin. Exact and local replication analyses were conducted in African Americans (n = 7990). The effects of sex, body mass index (BMI), and T2D on results were investigated through stratified analyses.

RESULTS: GWAS identified 39 significant (P value < 5 × 10

CONCLUSIONS: Our study identified genetic variants underlying variation in multiple adipocytokines, including the first loci for adipsin and ghrelin. We identified population differences in variants associated with adipocytokines and highlight the importance of stratification for discovery of loci. The high number of African-specific loci detected emphasizes the need for GWAS in African-ancestry populations, as these loci could not have been detected in other populations. Overall, our work contributes to the understanding of the biology linking adipocytokines to cardiometabolic traits.

© 2021. The Author(s).

Keywords: Adipocytokines; Africans; Cardiometabolic traits; GWAS; Obesity

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