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First Genome-Wide Association Study in an Australian Aboriginal Population Provides Insights into Genetic Risk Factors for Body Mass Index and Type 2 Diabetes

Lookup NU author(s): Professor Heather Cordell, Dr Elizabeth Davis



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


A body mass index (BMI) >22kg/m(2) 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 (rs10868204 P-genotyped = 1.50x10(-6); rs11140653 P-imputed_1000G = 2.90x10(-7)) 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 (rs12816270 P-genotyped = 8.06x10(-6); rs10841048 P-imputed_1000G = 6.28x10(-7)) was associated with BMI, but not with T2D as reported elsewhere. BMI also associated with CNTNAP2 (rs6960319 P-genotyped = 4.65x10(-5); rs13225016 P-imputed_1000G = 6.57x10(-5)), previously identified as the strongest gene-by-environment interaction for BMI in African-Americans. The top hit (rs11240074 P-genotyped = 5.59x10-6, P-imputed_1000G = 5.73x10(-6)) 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 (P-genotyped = 4.49x10(-4)) for BMI and IGF2BP2 P-imputed_1000G = 2.55x10(-6)) for T2D. Our results may provide novel functional leads in understanding disease pathogenesis in this Australian Aboriginal population.

Publication metadata

Author(s): Anderson D, Cordell HJ, Fakiola M, Francis RW, Syn G, Scaman ESH, Davis E, Miles SJ, McLeay T, Jamieson SE, Blackwell JM

Publication type: Article

Publication status: Published

Journal: PLoS One

Year: 2015

Volume: 10

Issue: 3

Online publication date: 11/03/2015

Acceptance date: 28/01/2015

Date deposited: 01/05/2015

ISSN (electronic): 1932-6203

Publisher: Public Library of Science


DOI: 10.1371/journal.pone.0119333


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Funder referenceFunder name
102858/Z/13/ZWellcome Trust
087436/Z/08/ZWellcome Trust
APP634301Australian National Health and Medical Research Council