Authors:
Anderson D, Cordell HJ, Fakiola M, Francis RW, Syn G, Scaman ESH, Davis E, Miles SJ, McLeay T, Jamieson SE, Blackwell JM
Authors notes:
PLoS ONE. 2015;10(3):e0119333
Keywords:
Body mass index, type 2 diabetes, Aboriginal, genome-wide association study
Abstract:
A body mass index (BMI) >22kg/m2 is a risk factor for type 2 diabetes (T2D) in Aboriginal Australians.
To identify loci associated with BMI and T2D we undertook a genome-wide association study using 1,075,436 quality-controlled single nucleotide polymorphisms (SNPs) genotyped (Illumina 2.5M Duo Beadchip) in 402 individuals in extended pedigrees from a Western Australian Aboriginal community.
Imputation using the thousand genomes (1000G) reference panel extended the analysis to 6,724,284 post quality-control autosomal SNPs.
No associations achieved genome-wide significance, commonly accepted as P<5x10-8.
Nevertheless, genes/pathways in common with other ethnicities were identified despite the arrival of Aboriginal people in Australia <45,000 years ago.
The top hit for BMI lies 5' of NTRK2, the type 2 neurotrophic tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF) that regulates energy balance downstream of melanocortin-4 receptor (MC4R).
PIK3C2G was associated with BMI, but not with T2D as reported elsewhere.
BMI also associated with CNTNAP2, previously identified as the strongest gene-by-environment interaction for BMI in African-Americans.
The top hit for T2D lies 5' of BCL9 that, along with TCF7L2, promotes beta-catenin's transcriptional activity in the WNT signaling pathway.
Additional hits occurred in genes affecting pancreatic (KCNJ6 , KCNA1) and/or GABA (GABRR1, KCNA1) functions.
Notable associations observed for genes previously identified at genome-wide significance in other populations included MC4R for BMI and IGF2BP2 for T2D.
Our results may provide novel functional leads in understanding disease pathogenesis in this Australian Aboriginal population.