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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.

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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