Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D-in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1-and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA.
Saxena
Richa
R
Voight
Benjamin F
BF
Lyssenko
Valeriya
V
Burtt
Noël P
NP
de Bakker
Paul I W
PI
Chen
Hong
H
Roix
Jeffrey J
JJ
Kathiresan
Sekar
S
Hirschhorn
Joel N
JN
Daly
Mark J
MJ
Hughes
Thomas E
TE
Groop
Leif
L
Altshuler
David
D
Almgren
Peter
P
Florez
Jose C
JC
Meyer
Joanne
J
Ardlie
Kristin
K
Bengtsson Boström
Kristina
K
Isomaa
Bo
B
Lettre
Guillaume
G
Lindblad
Ulf
U
Lyon
Helen N
HN
Melander
Olle
O
Newton-Cheh
Christopher
C
Nilsson
Peter
P
Orho-Melander
Marju
M
Råstam
Lennart
L
Speliotes
Elizabeth K
EK
Taskinen
Marja-Riitta
MR
Tuomi
Tiinamaija
T
Guiducci
Candace
C
Berglund
Anna
A
Carlson
Joyce
J
Gianniny
Lauren
L
Hackett
Rachel
R
Hall
Liselotte
L
Holmkvist
Johan
J
Laurila
Esa
E
Sjögren
Marketa
M
Sterner
Maria
M
Surti
Aarti
A
Svensson
Margareta
M
Svensson
Malin
M
Tewhey
Ryan
R
Blumenstiel
Brendan
B
Parkin
Melissa
M
Defelice
Matthew
M
Barry
Rachel
R
Brodeur
Wendy
W
Camarata
Jody
J
Chia
Nancy
N
Fava
Mary
M
Gibbons
John
J
Handsaker
Bob
B
Healy
Claire
C
Nguyen
Kieu
K
Gates
Casey
C
Sougnez
Carrie
C
Gage
Diane
D
Nizzari
Marcia
M
Gabriel
Stacey B
SB
Chirn
Gung-Wei
GW
Ma
Qicheng
Q
Parikh
Hemang
H
Richardson
Delwood
D
Ricke
Darrell
D
Purcell
Shaun
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D000483:Alleles; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D007438:Introns; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D014280:Triglycerides / Q000097:blood*
D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; C485100:GCKR protein, human; D005819:Genetic Markers; D018969:Insulin-Like Growth Factor Binding Proteins; D014280:Triglycerides