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

• Published in: Genome medicine 2021-10, Vol.13 (1), p.156-156, Article 156
• Main Authors: Meeks, Karlijn A C, Bentley, Amy R, Gouveia, Mateus H, Chen, Guanjie, Zhou, Jie, Lei, Lin, Adeyemo, Adebowale A, Doumatey, Ayo P, Rotimi, Charles N
• Format: Article
• Language: English
• Subjects: Adipocytokines; Adipokines; Adult; African Americans; African Americans - genetics; Africans; Analysis; Atherosclerosis; Biology; Blood pressure; Body Mass Index; Cardiometabolic traits; Cardiovascular disease; Cardiovascular Diseases - genetics; Cytokines; Cytokines - metabolism; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - genetics; Female; Gender differences; Gene loci; Genetic diversity; Genetic Predisposition to Disease - genetics; Genetic research; Genome-Wide Association Study; Genomes; Genomics; Ghrelin; Glucagon; Glucagon-like peptide 1; Glucose; GWAS; Hormones; Hormones - metabolism; Humans; Insulin; Insulin resistance; Interleukin 1; Interleukin 1 receptor antagonist; Interleukin 10; Interleukin 6; Interleukins; Leptin; Male; Middle Aged; Nigeria; Obesity; Obesity - genetics; Pathogenesis; Peptides; Phenotype; Plasminogen activator inhibitors; Quality control; Replication; Sleep apnea; Software; Type 2 diabetes; Urban areas
• ISSN: 1756-994X; 1756-994X
• DOI: 10.1186/s13073-021-00971-2

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. 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. GWAS identified 39 significant (P value