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Proc Natl Acad Sci U S A DOI:10.1073/pnas.1410428111

Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes.

Publication TypeJournal Article
Year of Publication2014
AuthorsMajithia, AR, Flannick, J, Shahinian, P, Guo, M, Bray, M-A, Fontanillas, P, Gabriel, SB, Rosen, ED, Altshuler, D
Corporate AuthorsGoT2D Consortium, NHGRI JHS/FHS Allelic Spectrum Project, SIGMA T2D Consortium, T2D-GENES Consortium
JournalProc Natl Acad Sci U S A
Volume111
Issue36
Pages13127-32
Date Published2014 Sep 09
ISSN1091-6490
KeywordsAdipocytes, Adult, Aged, Aged, 80 and over, Case-Control Studies, Cell Differentiation, Diabetes Mellitus, Type 2, Ethnic Groups, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, PPAR gamma, Risk Factors, Sequence Analysis, DNA
Abstract

Peroxisome proliferator-activated receptor gamma (PPARG) is a master transcriptional regulator of adipocyte differentiation and a canonical target of antidiabetic thiazolidinedione medications. In rare families, loss-of-function (LOF) mutations in PPARG are known to cosegregate with lipodystrophy and insulin resistance; in the general population, the common P12A variant is associated with a decreased risk of type 2 diabetes (T2D). Whether and how rare variants in PPARG and defects in adipocyte differentiation influence risk of T2D in the general population remains undetermined. By sequencing PPARG in 19,752 T2D cases and controls drawn from multiple studies and ethnic groups, we identified 49 previously unidentified, nonsynonymous PPARG variants (MAF

URLhttp://www.pnas.org/cgi/pmidlookup?view=long&pmid=25157153
DOI10.1073/pnas.1410428111
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25157153?dopt=Abstract

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID25157153
PubMed Central IDPMC4246964
Grant ListU01 DK085501 / DK / NIDDK NIH HHS / United States
5U01DK085526 / DK / NIDDK NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
HHSN268201300049C / / PHS HHS / United States
U01 DK085524 / DK / NIDDK NIH HHS / United States
U01 DK085545 / DK / NIDDK NIH HHS / United States
HHSN268201300048C / / PHS HHS / United States
K08 DK102877 / DK / NIDDK NIH HHS / United States
HHSN268201300047C / / PHS HHS / United States
U54HG003067 / HG / NHGRI NIH HHS / United States
HHSN268201300048C / HL / NHLBI NIH HHS / United States
BB/I02593X/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
HHSN268201300049C / HL / NHLBI NIH HHS / United States
R01 GM089652 / GM / NIGMS NIH HHS / United States
HHSN268201300050C / / PHS HHS / United States
RC2 DK088389 / DK / NIDDK NIH HHS / United States
HHSN268201300046C / / PHS HHS / United States
HHSN268201300047C / HL / NHLBI NIH HHS / United States
U01 DK085526 / DK / NIDDK NIH HHS / United States
HHSN268201300050C / HL / NHLBI NIH HHS / United States
U01 DK085584 / DK / NIDDK NIH HHS / United States
DK085584 / DK / NIDDK NIH HHS / United States
DK085545 / DK / NIDDK NIH HHS / United States
098395 / / Wellcome Trust / United Kingdom
R01 HL084553 / HL / NHLBI NIH HHS / United States
DK088389 / DK / NIDDK NIH HHS / United States
U01 DK062370 / DK / NIDDK NIH HHS / United States
DK085501 / DK / NIDDK NIH HHS / United States
HHSN268201300046C / HL / NHLBI NIH HHS / United States
GM089652 / GM / NIGMS NIH HHS / United States