Abstract
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.
Original language | English |
---|---|
Pages (from-to) | 77-81 |
Number of pages | 5 |
Journal | Nature Genetics |
Volume | 41 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 2009 |
Keywords
- GENOME-WIDE ASSOCIATION
- BETA-CELL FUNCTION
- GENE-EXPRESSION
- PLASMA-GLUCOSE
- RISK LOCI
- MELATONIN
- TRIGLYCERIDE
- REPLICATION
- HAPLOTYPE
- IMPACT
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Variants in MTNR1B influence fasting glucose levels. / Prokopenko, Inga; Langenberg, Claudia; Florez, Jose C.; Saxena, Richa; Soranzo, Nicole; Thorleifsson, Gudmar; Loos, Ruth J. F.; Manning, Alisa K.; Jackson, Anne U.; Aulchenko, Yurii; Potter, Simon C.; Erdos, Michael R.; Sanna, Serena; Hottenga, Jouke-Jan; Wheeler, Eleanor; Kaakinen, Marika; Lyssenko, Valeriya; Chen, Wei-Min; Ahmadi, Kourosh; Beckmann, Jacques S.; Bergman, Richard N.; Bochud, Murielle; Bonnycastle, Lori L.; Buchanan, Thomas A.; Cao, Antonio; Cervino, Alessandra; Coin, Lachlan; Collins, Francis S.; Crisponi, Laura; De Geus, Eco J. C.; Dehghan, Abbas; Deloukas, Panos; Doney, Alex S. F.; Elliott, Paul; Freimer, Nelson; Gateva, Vesela; Herder, Christian; Hofman, Albert; Hughes, Thomas E.; Hunt, Sarah; Illig, Thomas; Inouye, Michael; Isomaa, Bo; Johnson, Toby; Kong, Augustine; Krestyaninova, Maria; Kuusisto, Johanna; Laakso, Markku; Lim, Noha; Lindblad, Ulf; Lindgren, Cecilia M.; McCann, Owen T.; Mohlke, Karen L.; Morris, Andrew D.; Naitza, Silvia; Orru, Marco; Palmer, Colin N. A.; Pouta, Anneli; Randall, Joshua; Rathmann, Wolfgang; Saramies, Jouko; Scheet, Paul; Scott, Laura J.; Scuteri, Angelo; Sharp, Stephen; Sijbrands, Eric; Smit, Jan H.; Song, Kijoung; Steinthorsdottir, Valgerdur; Stringham, Heather M.; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Uitterlinden, Andre G.; Voight, Benjamin F.; Waterworth, Dawn; Wichmann, H-Erich; Willemsen, Gonneke; Witteman, Jacqueline C. M.; Yuan, Xin; Zhao, Jing Hua; Zeggini, Eleftheria; Schlessinger, David; Sandhu, Manjinder; Boomsma, Dorret I.; Uda, Manuela; Spector, Tim D.; Penninx, Brenda W. J. H.; Altshuler, David; Vollenweider, Peter; Jarvelin, Marjo Riitta; Lakatta, Edward; Waeber, Gerard; Fox, Caroline S.; Peltonen, Leena; Groop, Leif C.; Mooser, Vincent; Cupples, L. Adrienne; Thorsteinsdottir, Unnur; Boehnke, Michael; Barroso, Ines; Van Duijn, Cornelia; Dupuis, Josee; Watanabe, Richard M.; Stefansson, Kari; McCarthy, Mark I.; Wareham, Nicholas J.; Meigs, James B.; Abecasis, Goncalo R.
In: Nature Genetics, Vol. 41, No. 1, 01.2009, p. 77-81.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Variants in MTNR1B influence fasting glucose levels
AU - Prokopenko, Inga
AU - Langenberg, Claudia
AU - Florez, Jose C.
AU - Saxena, Richa
AU - Soranzo, Nicole
AU - Thorleifsson, Gudmar
AU - Loos, Ruth J. F.
AU - Manning, Alisa K.
AU - Jackson, Anne U.
AU - Aulchenko, Yurii
AU - Potter, Simon C.
AU - Erdos, Michael R.
AU - Sanna, Serena
AU - Hottenga, Jouke-Jan
AU - Wheeler, Eleanor
AU - Kaakinen, Marika
AU - Lyssenko, Valeriya
AU - Chen, Wei-Min
AU - Ahmadi, Kourosh
AU - Beckmann, Jacques S.
AU - Bergman, Richard N.
AU - Bochud, Murielle
AU - Bonnycastle, Lori L.
AU - Buchanan, Thomas A.
AU - Cao, Antonio
AU - Cervino, Alessandra
AU - Coin, Lachlan
AU - Collins, Francis S.
AU - Crisponi, Laura
AU - De Geus, Eco J. C.
AU - Dehghan, Abbas
AU - Deloukas, Panos
AU - Doney, Alex S. F.
AU - Elliott, Paul
AU - Freimer, Nelson
AU - Gateva, Vesela
AU - Herder, Christian
AU - Hofman, Albert
AU - Hughes, Thomas E.
AU - Hunt, Sarah
AU - Illig, Thomas
AU - Inouye, Michael
AU - Isomaa, Bo
AU - Johnson, Toby
AU - Kong, Augustine
AU - Krestyaninova, Maria
AU - Kuusisto, Johanna
AU - Laakso, Markku
AU - Lim, Noha
AU - Lindblad, Ulf
AU - Lindgren, Cecilia M.
AU - McCann, Owen T.
AU - Mohlke, Karen L.
AU - Morris, Andrew D.
AU - Naitza, Silvia
AU - Orru, Marco
AU - Palmer, Colin N. A.
AU - Pouta, Anneli
AU - Randall, Joshua
AU - Rathmann, Wolfgang
AU - Saramies, Jouko
AU - Scheet, Paul
AU - Scott, Laura J.
AU - Scuteri, Angelo
AU - Sharp, Stephen
AU - Sijbrands, Eric
AU - Smit, Jan H.
AU - Song, Kijoung
AU - Steinthorsdottir, Valgerdur
AU - Stringham, Heather M.
AU - Tuomi, Tiinamaija
AU - Tuomilehto, Jaakko
AU - Uitterlinden, Andre G.
AU - Voight, Benjamin F.
AU - Waterworth, Dawn
AU - Wichmann, H-Erich
AU - Willemsen, Gonneke
AU - Witteman, Jacqueline C. M.
AU - Yuan, Xin
AU - Zhao, Jing Hua
AU - Zeggini, Eleftheria
AU - Schlessinger, David
AU - Sandhu, Manjinder
AU - Boomsma, Dorret I.
AU - Uda, Manuela
AU - Spector, Tim D.
AU - Penninx, Brenda W. J. H.
AU - Altshuler, David
AU - Vollenweider, Peter
AU - Jarvelin, Marjo Riitta
AU - Lakatta, Edward
AU - Waeber, Gerard
AU - Fox, Caroline S.
AU - Peltonen, Leena
AU - Groop, Leif C.
AU - Mooser, Vincent
AU - Cupples, L. Adrienne
AU - Thorsteinsdottir, Unnur
AU - Boehnke, Michael
AU - Barroso, Ines
AU - Van Duijn, Cornelia
AU - Dupuis, Josee
AU - Watanabe, Richard M.
AU - Stefansson, Kari
AU - McCarthy, Mark I.
AU - Wareham, Nicholas J.
AU - Meigs, James B.
AU - Abecasis, Goncalo R.
PY - 2009/1
Y1 - 2009/1
N2 - 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.
AB - 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.
KW - GENOME-WIDE ASSOCIATION
KW - BETA-CELL FUNCTION
KW - GENE-EXPRESSION
KW - PLASMA-GLUCOSE
KW - RISK LOCI
KW - MELATONIN
KW - TRIGLYCERIDE
KW - REPLICATION
KW - HAPLOTYPE
KW - IMPACT
U2 - 10.1038/ng.290
DO - 10.1038/ng.290
M3 - Article
C2 - 19060907
VL - 41
SP - 77
EP - 81
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 1
ER -