Assessing the Role of 98 Established Loci for BMI in American Indians. Issue 5 (18th March 2019)

• Record Type: Journal Article
• Authors: Muller, Yunhua L.; Hanson, Robert L.; Piaggi, Paolo; Chen, Peng; Wiessner, Gregory; Okani, Chidinma; Skelton, Graham; Kobes, Sayuko; Hsueh, Wen‐Chi; Knowler, William C.; Bogardus, Clifton; Baier, Leslie J.
• Is Part Of: Obesity. Volume 27:Issue 5(2019)
• Page Start: 845
• Page End: 854
• Publication Date: 2019-03-18
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.22433
• Languages: English
• ISSNs: 1930-7381

Abstract

Abstract : Objective: Meta‐analyses of genome‐wide association studies in Europeans have identified > 98 loci for BMI. Transferability of these established associations in Pima Indians was analyzed. Methods: Among 98 lead single nucleotide polymorphisms (SNPs), 82 had minor allele frequency ≥ 0.01 in Pima Indians and were analyzed for association with the maximum BMI in adulthood ( n = 3, 491) and BMI z score in childhood ( n = 1, 958). Common tag SNPs across 98 loci were also analyzed for additional signals. Results: Among the lead SNPs, 13 ( TMEM18, TCF7L2, MRPS33P4, PRKD1, ZFP64, FTO, TAL1, CALCR, GNPDA2, CREB1, LMX1B, ADCY9, NLRC3 ) were associated with BMI ( P ≤ 0.05) in Pima adults. A multi‐allelic genetic risk score (GRS), which summed the risk alleles for 82 lead SNPs, showed a significant trend for a positive relationship between GRS and BMI in adulthood (beta = 0.48% per risk allele; P = 1.6 × 10 −9 ) and BMI z score in childhood (beta = 0.024 SD; P = 1.7 × 10 −7 ). GRS was significantly associated with BMI across all age groups ≥ 5 years, except for those ≥ 50 years. The strongest association was seen in adolescence (age 14‐16 years; P = 1.84 × 10 −9 ). Conclusions: In aggregate, European‐derived lead SNPs had a notable effect on BMI in Pima Indians. Polygenic obesity in this population manifests strongly in childhood and adolescence and persists throughout much of adult life.