Browsing by Author "Adebamowo, C.A."
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Item Genome-wide associated loci influencing interleukin (IL)-10, IL-1Ra, and IL-6 levels in African Americans(Immunogenetics, 2012-05) Ayele, F.T.; Doumatey, A.; Huang, H.; Zhou, J.; Charles, B.; Erdos, M.; Adeleye, J.; Balogun, W.; Fasanmade, O.; Johnson, T.; Oli, J.; Okafor, G.; Amoah, A.; Eghan Jr., B.A.; Agyenim-Boateng, K.; Acheampong, J.; Adebamowo, C.A.; Herbert, A.; Gerry, N.; Christman, M.; Chen, G.; Shriner, D.; Adeyemo, A.; Rotimi, C.N.Interleukins (ILs) are key mediators of the immune response and inflammatory process. Plasma levels of IL-10, IL-1Ra, and IL-6 are associated with metabolic conditions, show large inter-individual variations, and are under strong genetic control. Therefore, elucidation of the genetic variants that influence levels of these ILs provides useful insights into mechanisms of immune response and pathogenesis of diseases. We conducted a genome-wide association study (GWAS) of IL-10, IL-1Ra, and IL-6 levels in 707 nondiabetic African Americans using 5,396,780 imputed and directly genotyped single nucleotide polymorphisms (SNPs) with adjustment for gender, age, and body mass index. IL-10 levels showed genome-wide significant associations (p<5× 10 -8) with eight SNPs, the most significant of which was rs5743185 in the PMS1 gene (p=2.30×10 -10). We tested replication of SNPs that showed genome-wide significance in 425 non-diabetic individuals from West Africa, and successfully replicated rs17365948 in the YWHAZ gene (p= 0.02). IL-1Ra levels showed suggestive associations with two SNPs in the ASB3 gene (p=2.55×10 -7), ten SNPs in the IL-1 gene family (IL1F5, IL1F8, IL1F10, and IL1Ra, p= 1.04×10 -6 to 1.75×10 -6), and 23 SNPs near the IL1A gene (p=1.22×10 -6 to 1.63×10 -6).We also successfully replicated rs4251961 (p=0.009); this SNP was reported to be associated with IL-1Ra levels in a candidate gene study of Europeans. IL-6 levels showed genome-wide significant association with one SNP (RP11-314E23.1; chr6:133397598; p= 8.63×10 -9). To our knowledge, this is the first GWAS on IL-10, IL-1Ra, and IL-6 levels. Follow-up of these findings may provide valuable insight into the pathobiology of IL actions and dysregulations in inflammation and human diseases.Item Polygenic risk scores for CARDINAL study(nature, 2022) Adebamowo, C.A.; Adeyemo, A.; Ashaye, A.; Akpa, O.M.; Chikowore, T.; Choudhury, A.; Fakim, Y.J.; Fatumo, S.; Hanchard, N.; Hauser, M.; Mitchell, B.; Mulder, N.; Ofori-Acquah, S.F.; Owolabi, M.; Ramsay, M.; Tayo, B.; VasanthKumar, A.B.; Zhang, Y.; Adebamowo, S.N.Item Relationships among obesity, inflammation, and insulin resistance in african americans and west africans(Obesity, 2010-03) Doumatey, A.P.; Lashley, K.S.; Huang, H.; Zhou, J.; Chen, G.; Amoah, A.; Agyenim-Boateng, K.; Oli, J.; Fasanmade, O.; Adebamowo, C.A.; Adeyemo, A.A.; Rotimi, C.N.Several research studies in different populations indicate that inflammation may be the link between obesity and insulin resistance (IR). However, this relationship has not been adequately explored among African Americans, an ethnic group with disproportionately high rates of obesity and IR. In this study, we conducted a comparative study of the relationship among adiposity, inflammation, and IR in African Americans and West Africans, the ancestral source population for African Americans. The associations between obesity markers (BMI and waist-to-hip ratio (WHR)), inflammatory markers (high-sensitivity C-reactive protein (hsCRP), haptoglobin, interleukin (IL)-6, and tumor necrosis factor (TNF)-α), and IR (homeostasis model assessment of insulin resistance (HOMA IR)) were evaluated in 247 West Africans and 315 African Americans. In average, African Americans were heavier than the West Africans (by an average of 1.6 BMI units for women and 3 BMI units for men). Plasma hsCRP, haptoglobin, and IL-6 (but not TNF-α level) were higher in African Americans than in West Africans. In both populations, BMI was associated with markers of inflammation and with HOMA IR, and these associations remained significant after adjusting for sex and age. However, the pattern of associations between measured inflammatory markers and IR was different between the two groups. In West Africans, hsCRP was the only inflammatory marker associated with IR. In contrast, hsCRP, haptoglobin, and IL-6 were all associated with IR in African Americans. Interestingly, none of the associations between markers of inflammation and IR remained significant after adjusting for BMI. This finding suggests that in African Americans, the relationship between inflammatory markers and IR is mediated by adiposity.