Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes.
The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 x 10(-7) between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 (P(follow-up) <or= 1.35 x 10(-9); P(overall) <or= 1.15 x 10(-14)), leaving eight regions with small effects or false-positive associations. We also obtained evidence for chromosome 18q22 (P(overall) = 1.38 x 10(-8)) from a GWA study of nonsynonymous SNPs. Several regions, including 18q22 and 18p11, showed association with autoimmune thyroid disease. This study increases the number of T1D loci with compelling evidence from six to at least ten.
Todd
John A
JA
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0XY, UK. john.todd@cimr.cam.ac.uk
Walker
Neil M
NM
Cooper
Jason D
JD
Smyth
Deborah J
DJ
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Kate
K
Plagnol
Vincent
V
Bailey
Rebecca
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Nejentsev
Sergey
S
Field
Sarah F
SF
Payne
Felicity
F
Lowe
Christopher E
CE
Szeszko
Jeffrey S
JS
Hafler
Jason P
JP
Zeitels
Lauren
L
Yang
Jennie H M
JH
Vella
Adrian
A
Nutland
Sarah
S
Stevens
Helen E
HE
Schuilenburg
Helen
H
Coleman
Gillian
G
Maisuria
Meeta
M
Meadows
William
W
Smink
Luc J
LJ
Healy
Barry
B
Burren
Oliver S
OS
Lam
Alex A C
AA
Ovington
Nigel R
NR
Allen
James
J
Adlem
Ellen
E
Leung
Hin-Tak
HT
Wallace
Chris
C
Howson
Joanna M M
JM
Guja
Cristian
C
Ionescu-Tîrgovişte
Constantin
C
Simmonds
Matthew J
MJ
Heward
Joanne M
JM
Gough
Stephen C L
SC
Dunger
David B
DB
Wicker
Linda S
LS
Clayton
David G
DG
D000293:Adolescent; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D020641:Polymorphism, Single Nucleotide