Assessing FOXO1A as a potential susceptibility locus for type 2 diabetes and obesity in American Indians. (4th September 2015)

• Record Type: Journal Article
• Authors: Muller, Yunhua L.; Hanson, Robert L.; Wiessner, Gregory; Nieboer, Lori; Kobes, Sayuko; Piaggi, Paolo; Abdussamad, Mahdi; Okani, Chidinma; Knowler, William C.; Bogardus, Clifton; Baier, Leslie J.
• Is Part Of: Obesity. Volume 23:Number 10(2015:Oct.)
• Page Start: 1960
• Page End: 1965
• Publication Date: 2015-09-04
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.21236
• Languages: English
• ISSNs: 1930-7381

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="oby21236-sec-0001" sec-type="section"> <title>Objective</title> <p>A prior genome‐wide association study (GWAS) in Pima Indians identified variation within <italic>FOXO1A</italic> that modestly associated with early‐onset (onset age <25years) type 2 diabetes (T2D). <italic>FOXO1A</italic> encodes the forkhead transcription factor involved in pancreatic β‐cell growth and hypothalamic energy balance; therefore, <italic>FOXO1A</italic> was analyzed as a candidate gene for T2D and obesity in a population‐based sample of 7, 710 American Indians.</p> </sec> <sec id="oby21236-sec-0002" sec-type="section"> <title>Methods</title> <p>Tag SNPs in/near <italic>FOXO1A</italic> (minor allele frequency≥0.05) were analyzed for association with T2D at early onset (<italic>n</italic> = 1, 060) and all ages (<italic>n</italic> = 7, 710) and with insulin secretion (<italic>n</italic> = 298). SNPs were also analyzed for association with maximum body mass index (BMI) in adulthood (<italic>n</italic> = 5, 918), maximum BMI <italic>z</italic>‐score in childhood (<italic>n</italic> = 5, 350), and % body fat (<italic>n</italic> = 555).</p> </sec> <sec id="oby21236-sec-0003" sec-type="section"> <title>Results</title> <p>An intronic SNP rs2297627 associated with early‐onset T2D [OR = 1.34 (1.13‐1.58), <italic>P</italic> = 8.7 × 10<sup>−4</sup>] and T2D onset at any age [OR = 1.19 (1.09‐1.30), <italic>P</italic> = 1 × 10<sup>−4</sup>]. The T2D risk allele also associated with lower acute insulin secretion (<italic>β</italic> = 0.88, as a multiplier<italic>, P</italic> = 0.02). Another intronic SNP (rs1334241, <italic>D</italic>′ = 0.99, <italic>r</italic><sup>2</sup> = 0.49 with rs2297627) associated with maximum adulthood BMI (<italic>β</italic> = 1.02, as a multiplier, <italic>P</italic> = 3 × 10<sup>−5</sup>), maximum childhood BMI <italic>z</italic>‐score (<italic>β</italic> = 0.08, <italic>P</italic> = 3 × 10<sup>−4</sup>), and % body fat (<italic>β</italic> = 0.83%, <italic>P</italic> = 0.04).</p> </sec> <sec id="oby21236-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Common variation in <italic>FOXO1A</italic> may modestly affect risk for T2D and obesity in American Indians.</p> </sec> </abstract>