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Assessing the Role of 98 Established Loci for BMI in American Indians
Author(s) -
Muller Yunhua L.,
Hanson Robert L.,
Piaggi Paolo,
Chen Peng,
Wiessner Gregory,
Okani Chidinma,
Skelton Graham,
Kobes Sayuko,
Hsueh WenChi,
Knowler William C.,
Bogardus Clifton,
Baier Leslie J.
Publication year - 2019
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.22433
Subject(s) - single nucleotide polymorphism , fto gene , demography , obesity , allele , medicine , minor allele frequency , genetic association , body mass index , genetics , biology , genotype , gene , sociology
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.