PMID- 25760438
OWN - NLM
STAT- MEDLINE
DCOM- 20151130
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 3
DP  - 2015
TI  - First genome-wide association study in an Australian aboriginal population 
      provides insights into genetic risk factors for body mass index and type 2 
      diabetes.
PG  - e0119333
LID - 10.1371/journal.pone.0119333 [doi]
LID - e0119333
AB  - 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 = 
      4.65x10-5; rs13225016 Pimputed_1000G = 6.57x10-5), previously identified as the 
      strongest gene-by-environment interaction for BMI in African-Americans. The top 
      hit (rs11240074 Pgenotyped = 5.59x10-6, Pimputed_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 (Pgenotyped = 4.49x10-4) for BMI 
      and IGF2BP2 Pimputed_1000G = 2.55x10-6) for T2D. Our results may provide novel 
      functional leads in understanding disease pathogenesis in this Australian 
      Aboriginal population.
FAU - Anderson, Denise
AU  - Anderson D
AD  - Telethon Kids Institute, The University of Western Australia, Subiaco, Western 
      Australia, 6008, Australia.
FAU - Cordell, Heather J
AU  - Cordell HJ
AD  - Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 
      3BZ, United Kingdom.
FAU - Fakiola, Michaela
AU  - Fakiola M
AD  - Telethon Kids Institute, The University of Western Australia, Subiaco, Western 
      Australia, 6008, Australia; Cambridge Institute for Medical Research, Department 
      of Medicine, and Department of Pathology, University of Cambridge, Cambridge, 
      United Kingdom.
FAU - Francis, Richard W
AU  - Francis RW
AD  - Telethon Kids Institute, The University of Western Australia, Subiaco, Western 
      Australia, 6008, Australia.
FAU - Syn, Genevieve
AU  - Syn G
AD  - Telethon Kids Institute, The University of Western Australia, Subiaco, Western 
      Australia, 6008, Australia.
FAU - Scaman, Elizabeth S H
AU  - Scaman ES
AD  - Telethon Kids Institute, The University of Western Australia, Subiaco, Western 
      Australia, 6008, Australia.
FAU - Davis, Elizabeth
AU  - Davis E
AD  - Telethon Kids Institute, The University of Western Australia, Subiaco, Western 
      Australia, 6008, Australia; Department of Endocrinology and Diabetes, Princess 
      Margaret Hospital for Children, Subiaco, Western Australia, 6008, Australia.
FAU - Miles, Simon J
AU  - Miles SJ
AD  - Ngangganawili Aboriginal Health Service, Wiluna, Western Australia, 6646, 
      Australia.
FAU - McLeay, Toby
AU  - McLeay T
AD  - Ngangganawili Aboriginal Health Service, Wiluna, Western Australia, 6646, 
      Australia.
FAU - Jamieson, Sarra E
AU  - Jamieson SE
AD  - Telethon Kids Institute, The University of Western Australia, Subiaco, Western 
      Australia, 6008, Australia.
FAU - Blackwell, Jenefer M
AU  - Blackwell JM
AD  - Telethon Kids Institute, The University of Western Australia, Subiaco, Western 
      Australia, 6008, Australia; Cambridge Institute for Medical Research, Department 
      of Medicine, and Department of Pathology, University of Cambridge, Cambridge, 
      United Kingdom.
LA  - eng
GR  - Wellcome Trust/United Kingdom
GR  - 087436/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150311
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Australia/ethnology
MH  - Body Mass Index
MH  - Diabetes Mellitus, Type 2/*ethnology/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study/*methods
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Native Hawaiian or Other Pacific Islander/ethnology/*genetics
MH  - Pedigree
MH  - *Polymorphism, Single Nucleotide
MH  - Risk Factors
PMC - PMC4356593
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/03/12 06:00
MHDA- 2015/12/15 06:00
PMCR- 2015/03/11
CRDT- 2015/03/12 06:00
PHST- 2014/08/02 00:00 [received]
PHST- 2015/01/28 00:00 [accepted]
PHST- 2015/03/12 06:00 [entrez]
PHST- 2015/03/12 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2015/03/11 00:00 [pmc-release]
AID - PONE-D-14-34385 [pii]
AID - 10.1371/journal.pone.0119333 [doi]
PST - epublish
SO  - PLoS One. 2015 Mar 11;10(3):e0119333. doi: 10.1371/journal.pone.0119333. 
      eCollection 2015.