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Imamura, M.* ; Maeda, S.* ; Yamauchi, T.* ; Hara, K.* ; Yasuda, K.* ; Morizono, T.* ; Takahashi, A.* ; Horikoshi, M.* ; Nishimura, M.* ; Fujita, H.* ; Tsunoda, T.* ; Kubo, M.* ; Watada, H.* ; Maegawa, H.* ; Okada-Iwabu, M.* ; Iwabu, M.* ; Shojima, N.* ; Ohshige, T.* ; Omori, S.* ; Iwata, M.* ; Hirose, H.* ; Kaku, K.* ; Ito, C.* ; Tanaka, Y.* ; Tobe, K.* ; Kashiwagi, A.* ; Kawamori, R.* ; DIAGRAM Consortium (Huth, C. ; Grallert, H. ; Gieger, C. ; Klopp, N. ; Meitinger, T. ; Petersen, A.-K. ; Thorand, B. ; Wichmann, H.-E. ; Illig, T.) ; Kasuga, M.* ; Kamatani, N.*

A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations.

Hum. Mol. Genet. 21, 3042-3049 (2012)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
To identify a novel susceptibility locus for type 2 diabetes, we performed an imputation-based, genome-wide association study (GWAS) in a Japanese population using newly obtained imputed-genotype data for 2 229 890 single-nucleotide polymorphisms (SNPs) estimated from previously reported, directly genotyped GWAS data in the same samples (stage 1: 4470 type 2 diabetes versus 3071 controls). We directly genotyped 43 new SNPs with P-values of <10(-4) in a part of stage-1 samples (2692 type 2 diabetes versus 3071 controls), and the associations of validated SNPs were evaluated in another 11 139 Japanese individuals (stage 2: 7605 type 2 diabetes versus 3534 controls). Combined meta-analysis using directly genotyped data for stages 1 and 2 revealed that rs515071 in ANK1 and rs7656416 near MGC21675 were associated with type 2 diabetes in the Japanese population at the genome-wide significant level (P < 5 × 10(-8)). The association of rs515071 was also observed in European GWAS data (combined P for all populations = 6.14 × 10(-10)). Rs7656416 was in linkage disequilibrium to rs6815464, which had recently been identified as a top signal in a meta-analysis of East Asian GWAS for type 2 diabetes (r(2) = 0.76 in stage 2). The association of rs7656416 with type 2 diabetes disappeared after conditioning on rs6815464. These results indicate that the ANK1 locus is a new, common susceptibility locus for type 2 diabetes across different ethnic groups. The signal of association was weaker in the directly genotyped data, so the improvement in signal indicates the importance of imputation in this particular case.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter GENOME-WIDE ASSOCIATION; LARGE-SCALE ASSOCIATION; INTRAMUSCULAR FAT; RISK LOCI; GENE; REPLICATION; VARIANTS; ANKYRIN-1; PATHWAYS; PROMOTER
Sprache englisch
Veröffentlichungsjahr 2012
HGF-Berichtsjahr 2012
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Zeitschrift Human Molecular Genetics
Quellenangaben Band: 21, Heft: 13, Seiten: 3042-3049 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Research Unit Molecular Epidemiology (AME)
Institute of Genetic Epidemiology (IGE)
POF Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30503 - Chronic Diseases of the Lung and Allergies
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504000-002
G-504200-002
G-504100-001
G-503900-001
G-503900-002
PubMed ID 22456796
DOI 10.1093/hmg/dds113
WOS ID WOS:000305457700017
Erfassungsdatum 2012-11-08
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