Variants in MTNR1B influence fasting glucose levels.
To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
Prokopenko
Inga
I
[1] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [3] These authors contributed equally to this work.
Langenberg
Claudia
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Jose C
JC
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Richa
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N
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Gudmar
G
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RJ
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Alisa K
AK
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AU
Aulchenko
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Potter
Simon C
SC
Erdos
Michael R
MR
Sanna
Serena
S
Hottenga
Jouke-Jan
JJ
Wheeler
Eleanor
E
Kaakinen
Marika
M
Lyssenko
Valeriya
V
Chen
Wei-Min
WM
Ahmadi
Kourosh
K
Beckmann
Jacques S
JS
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Richard N
RN
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Murielle
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Lori L
LL
Buchanan
Thomas A
TA
Cao
Antonio
A
Cervino
Alessandra
A
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Lachlan
L
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Francis S
FS
Crisponi
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Eco J C
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AS
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Gateva
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V
Herder
Christian
C
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A
Hughes
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TE
Hunt
Sarah
S
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Isomaa
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Toby
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Augustine
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Krestyaninova
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Johanna
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Markku
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Noha
N
Lindblad
Ulf
U
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Cecilia M
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Karen L
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Andrew D
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Naitza
Silvia
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Marco
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Palmer
Colin N A
CN
Pouta
Anneli
A
Randall
Joshua
J
Rathmann
Wolfgang
W
Saramies
Jouko
J
Scheet
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LJ
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Stephen
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Eric
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Jan H
JH
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Steinthorsdottir
Valgerdur
V
Stringham
Heather M
HM
Tuomi
Tiinamaija
T
Tuomilehto
Jaakko
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Uitterlinden
André G
AG
Voight
Benjamin F
BF
Waterworth
Dawn
D
Wichmann
H-Erich
HE
Willemsen
Gonneke
G
Witteman
Jacqueline C M
JC
Yuan
Xin
X
Zhao
Jing Hua
JH
Zeggini
Eleftheria
E
Schlessinger
David
D
Sandhu
Manjinder
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Boomsma
Dorret I
DI
Uda
Manuela
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Spector
Tim D
TD
Penninx
Brenda Wjh
BW
Altshuler
David
D
Vollenweider
Peter
P
Jarvelin
Marjo Riitta
MR
Lakatta
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E
Waeber
Gerard
G
Fox
Caroline S
CS
Peltonen
Leena
L
Groop
Leif C
LC
Mooser
Vincent
V
Cupples
L Adrienne
LA
Thorsteinsdottir
Unnur
U
Boehnke
Michael
M
Barroso
Inês
I
Van Duijn
Cornelia
C
Dupuis
Josée
J
Watanabe
Richard M
RM
Stefansson
Kari
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Mark I
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Wareham
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D001786:Blood Glucose / Q000235:genetics*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D005215:Fasting / Q000097:blood*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D044123:Receptor, Melatonin, MT2 / Q000235:genetics*; D044094:Receptors, Melatonin / Q000235:genetics*
D001786:Blood Glucose; D044123:Receptor, Melatonin, MT2; D044094:Receptors, Melatonin