First genome-wide association study in an Australian aboriginal population provides insights into genetic risk factors for body mass index and type 2 diabetes

PloS One
Denise AndersonJenefer M Blackwell

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 (rs10868204 Pgenotyped = 1.50x10-6; rs11140653 Pimputed_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 Pgenotyped = 8.06x10-6; rs10841048 Pimputed_1000G = 6.28x10-7) was associated with BMI, but not with T2D as reported elsewhere. BMI also associated with CNTNAP2 (rs6960319 Pgenotyped...Continue Reading

References

Jun 9, 1997·Biochemical and Biophysical Research Communications·L K HoM J Fry
May 5, 1999·Journal of Medical Ethics·M Dodson, R Williamson
Jan 13, 2000·American Journal of Human Genetics·G R AbecasisW O Cookson
Nov 4, 2000·The American Journal of Clinical Nutrition·R J Kuczmarski, K M Flegal
Apr 21, 2001·Biometrics·B Devlin, K Roeder
Feb 28, 2002·American Journal of Epidemiology·W James Gauderman
Mar 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Daiya Takai, Peter A Jones
May 15, 2002·Diabetes Research and Clinical Practice·M DanielK O'Dea
Mar 4, 2003·Nature Neuroscience·Paco S HersonJames Maylie
Mar 26, 2003·Genome Research·Michael BrudnoSerafim Batzoglou
Dec 25, 2003·BMC Bioinformatics·Michael BrudnoBurkhard Morgenstern
Jan 22, 2004·Bioinformatics·Emmanuel ParadisKorbinian Strimmer
Mar 24, 2004·Trends in Endocrinology and Metabolism : TEM·Christian J GruberJohannes C Huber
May 20, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jorge M NaciffGeorge P Daston
Oct 4, 2005·Lancet·David W Haslam, W Philip T James
Aug 29, 2006·Nature Structural & Molecular Biology·Nuo Yang, Haig H Kazazian
Oct 28, 2006·Nucleic Acids Research·Tu Minh PhuongSerafim Batzoglou
Dec 30, 2006·PLoS Genetics·Nick PattersonDavid Reich
Mar 27, 2007·Bioinformatics·Yurii S AulchenkoCornelia M van Duijn
Aug 3, 2007·The Journal of Clinical Investigation·Valeriya LyssenkoLeif Groop
Aug 11, 2007·Social Science & Medicine·Grant Gillett, Felicity McKergow
Oct 10, 2007·American Journal of Human Genetics·Wei-Min Chen, Goncalo R Abecasis
Nov 10, 2007·Biochemical and Biophysical Research Communications·Makoto DaimonTakeo Kato
Feb 27, 2008·Genetic Epidemiology·Frank Dudbridge, Arief Gusnanto
May 6, 2008·Nature Genetics·Ruth J F LoosKaren L Mohlke
Jul 29, 2008·BMC Medical Genetics·Osama AlsmadiBrian F Meyer
Dec 17, 2008·Nature Genetics·Cristen J WillerUNKNOWN Genetic Investigation of ANthropometric Traits Consortium
Jan 21, 2010·American Journal of Human Genetics·Koji OkamotoKatsushi Tokunaga

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Citations

Oct 5, 2016·Molecular Aspects of Medicine·Hanah RodriguezAssam El-Osta
Feb 6, 2017·Genomics & Informatics·Sungkyoung ChoiTaesung Park
Jul 7, 2019·Reviews in Endocrine & Metabolic Disorders·Malgorzata Monika BrzozowskaMurray P Cox
Jan 1, 2015·Journal of Diabetes and Metabolic Disorders·Amir T IbrahimHiba S Mohamed
Jun 19, 2018·Frontiers in Physiology·Sander A J VerbruggeHenning Wackerhage
Aug 8, 2019·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Fatou K NdiayeAmélie Bonnefond
Mar 20, 2019·Biomolecules·Jean Piero MargariaEmilio Hirsch
Dec 15, 2020·The International Journal of Neuropsychopharmacology·Yutaka MizukiNorihito Yamada
Mar 12, 2021·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Sarra E JamiesonJenefer M Blackwell

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Datasets Mentioned

BETA
EGAS00001001004

Methods Mentioned

BETA
PCA
chips
acetylation

Software Mentioned

Ensembl
R package SITAR
LAGAN
AliBaba
GenABEL
LocusZoom
FASTA
DICER
CpG
R package GenABEL

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