Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium.
Type 2 diabetes (T2D) is a common, polygenic chronic disease with high heritability. The purpose of this whole-genome association study was to discover novel T2D-associated genes. We genotyped 500 familial cases and 497 controls with >300,000 HapMap-derived tagging single-nucleotide-polymorphism (SNP) markers. When a stringent statistical correction for multiple testing was used, the only significant SNP was at TCF7L2, which has already been discovered and confirmed as a T2D-susceptibility gene. For a replication study, we selected 10 SNPs in six chromosomal regions with the strongest association (singly or as part of a haplotype) for retesting in an independent case-control set including 2,573 T2D cases and 2,776 controls. The most significant replicated result was found at the AHI1-LOC441171 gene region.
Salonen
Jukka T
JT
Oy Jurilab, and Research Institute of Public Health, University of Kuopio, Kuopio, Finland, and Hope Hospital, Salford, UK.
Uimari
Pekka
P
Aalto
Juha-Matti
JM
Pirskanen
Mia
M
Kaikkonen
Jari
J
Todorova
Boryana
B
Hyppönen
Jelena
J
Korhonen
Veli-Pekka
VP
Asikainen
Janne
J
Devine
Christopher
C
Tuomainen
Tomi-Pekka
TP
Luedemann
Jan
J
Nauck
Matthias
M
Kerner
Wolfgang
W
Stephens
Richard H
RH
New
John P
JP
Ollier
William E
WE
Gibson
J Martin
JM
Payton
Antony
A
Horan
Michael A
MA
Pendleton
Neil
N
Mahoney
Walt
W
Meyre
David
D
Delplanque
Jerôme
J
Froguel
Philippe
P
Luzzatto
Oren
O
Yakir
Benjamin
B
Darvasi
Ariel
A
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004739:England; D005260:Female; D005387:Finland; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005858:Germany; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044465:White People
C487178:AHI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport