TY - JOUR
T1 - Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
AU - GIANT Consortium, MAGIC Investigators
AU - Voight, Benjamin F.
AU - Scott, Laura J.
AU - Steinthorsdottir, Valgerdur
AU - Morris, Andrew P.
AU - Dina, Christian
AU - Welch, Ryan P.
AU - Zeggini, Eleftheria
AU - Huth, Cornelia
AU - Aulchenko, Yurii S.
AU - Thorleifsson, Gudmar
AU - McCulloch, Laura
AU - Ferreira, Teresa
AU - Grallert, Harald
AU - Amin, Najaf
AU - Wu, Guanming
AU - Willer, Cristen J.
AU - Raychaudhuri, Soumya
AU - McCarroll, Steve A.
AU - Langenberg, Claudia
AU - Hofmann, Oliver M.
AU - Dupuis, Josee
AU - Qi, Lu
AU - Segre, Ayellet V.
AU - van Hoek, Mandy
AU - Navarro, Pau
AU - Ardlie, Kristin
AU - Balkau, Beverley
AU - Benediktsson, Rafn
AU - Bennett, Amanda J.
AU - Blagieva, Roza
AU - Boerwinkle, Eric
AU - Bonnycastle, Lori L.
AU - Bostrom, Kristina Bengtsson
AU - Bravenboer, Bert
AU - Bumpstead, Suzannah
AU - Burtt, Noisel P.
AU - Charpentier, Guillaume
AU - Chines, Peter S.
AU - Cornelis, Marilyn
AU - Couper, David J.
AU - Crawford, Gabe
AU - Doney, Alex S. F.
AU - Elliott, Katherine S.
AU - Elliott, Amanda L.
AU - Erdos, Michael R.
AU - Fox, Caroline S.
AU - Morris, Andrew
AU - Rudan, Igor
AU - Campbell, Harry
AU - Wilson, James F.
PY - 2010/7
Y1 - 2010/7
N2 - By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
AB - By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
KW - Polymorphism, Single Nucleotide
KW - Genome, Human
KW - Humans
KW - Fasting
KW - Genetic Heterogeneity
KW - Blood Glucose
KW - Genome-Wide Association Study
KW - Gene Expression Profiling
KW - Dual-Specificity Phosphatases
KW - KCNQ1 Potassium Channel
KW - Diabetes Mellitus, Type 2
KW - Mitogen-Activated Protein Kinase Phosphatases
KW - Hepatocyte Nuclear Factor 1-alpha
KW - Genetic Predisposition to Disease
KW - Gene Dosage
KW - Meta-Analysis as Topic
UR - http://www.scopus.com/inward/record.url?scp=77954143522&partnerID=8YFLogxK
U2 - 10.1038/ng.609
DO - 10.1038/ng.609
M3 - Article
C2 - 20581827
SN - 1061-4036
VL - 42
SP - 579-U155
JO - Nature Genetics
JF - Nature Genetics
IS - 7
ER -