Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Benjamin F. Voight; Laura J. Scott; Valgerdur Steinthorsdottir; Andrew P. Morris; Christian Dina; Ryan P. Welch; Eleftheria Zeggini; Cornelia Huth; Yurii S. Aulchenko; Gudmar Thorleifsson; Laura J. McCulloch; Teresa Ferreira; Harald Grallert; Najaf Amin; Guanming Wu; Cristen J. Willer; Soumya Raychaudhuri; Steve A. McCarroll; Claudia Langenberg; Oliver M. Hofmann; Josee Dupuis; Lu Qi; Ayellet V. Segre; Mandy van Hoek; Pau Navarro; Kristin Ardlie; Beverley Balkau; Rafn Benediktsson; Amanda J. Bennett; Roza Blagieva; Eric Boerwinkle; Lori L. Bonnycastle; Kristina Bengtsson Bostrom; Bert Bravenboer; Suzannah Bumpstead; Noisel P. Burtt; Guillaume Charpentier; Peter S. Chines; Marilyn Cornelis; David J. Couper; Gabe Crawford; Alex S. F. Doney; Katherine S. Elliott; Amanda L. Elliott; Michael R. Erdos; Caroline S. Fox; Christopher S. Franklin; Martha Ganser; Andrew D. Morris; Colin N. A. Palmer; GIANT Consortium, MAGIC Investigators

doi:10.1038/ng.609

Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Benjamin F. Voight, Laura J. Scott, Valgerdur Steinthorsdottir, Andrew P. Morris, Christian Dina, Ryan P. Welch, Eleftheria Zeggini, Cornelia Huth, Yurii S. Aulchenko, Gudmar Thorleifsson, Laura J. McCulloch, Teresa Ferreira, Harald Grallert, Najaf Amin, Guanming Wu, Cristen J. Willer, Soumya Raychaudhuri, Steve A. McCarroll, Claudia Langenberg, Oliver M. HofmannJosee Dupuis, Lu Qi, Ayellet V. Segre, Mandy van Hoek, Pau Navarro, Kristin Ardlie, Beverley Balkau, Rafn Benediktsson, Amanda J. Bennett, Roza Blagieva, Eric Boerwinkle, Lori L. Bonnycastle, Kristina Bengtsson Bostrom, Bert Bravenboer, Suzannah Bumpstead, Noisel P. Burtt, Guillaume Charpentier, Peter S. Chines, Marilyn Cornelis, David J. Couper, Gabe Crawford, Alex S. F. Doney, Katherine S. Elliott, Amanda L. Elliott, Michael R. Erdos, Caroline S. Fox, Christopher S. Franklin, Martha Ganser, Andrew D. Morris, Colin N. A. Palmer, GIANT Consortium, MAGIC Investigators

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Abstract

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.

Original language	English
Pages (from-to)	579-U155
Number of pages	13
Journal	Nature Genetics
Volume	42
Issue number	7
DOIs	https://doi.org/10.1038/ng.609
Publication status	Published - Jul 2010

Keywords

GENOME-WIDE ASSOCIATION
C-REACTIVE PROTEIN
FASTING PLASMA-GLUCOSE
QT INTERVAL DURATION
INSULIN-RESISTANCE
COMMON VARIANTS
COMPLEX DISEASES
GENE-EXPRESSION
HNF1-ALPHA GENE
CROHNS-DISEASE

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Voight, B. F., Scott, L. J., Steinthorsdottir, V., Morris, A. P., Dina, C., Welch, R. P., Zeggini, E., Huth, C., Aulchenko, Y. S., Thorleifsson, G., McCulloch, L. J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C. J., Raychaudhuri, S., McCarroll, S. A., Langenberg, C., ... GIANT Consortium, MAGIC Investigators (2010). Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nature Genetics, 42(7), 579-U155. https://doi.org/10.1038/ng.609

@article{e6e974a56e354687927ab1ae364f49f5,

title = "Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis",

abstract = "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.",

keywords = "GENOME-WIDE ASSOCIATION, C-REACTIVE PROTEIN, FASTING PLASMA-GLUCOSE, QT INTERVAL DURATION, INSULIN-RESISTANCE, COMMON VARIANTS, COMPLEX DISEASES, GENE-EXPRESSION, HNF1-ALPHA GENE, CROHNS-DISEASE",

author = "Voight, {Benjamin F.} and Scott, {Laura J.} and Valgerdur Steinthorsdottir and Morris, {Andrew P.} and Christian Dina and Welch, {Ryan P.} and Eleftheria Zeggini and Cornelia Huth and Aulchenko, {Yurii S.} and Gudmar Thorleifsson and McCulloch, {Laura J.} and Teresa Ferreira and Harald Grallert and Najaf Amin and Guanming Wu and Willer, {Cristen J.} and Soumya Raychaudhuri and McCarroll, {Steve A.} and Claudia Langenberg and Hofmann, {Oliver M.} and Josee Dupuis and Lu Qi and Segre, {Ayellet V.} and {van Hoek}, Mandy and Pau Navarro and Kristin Ardlie and Beverley Balkau and Rafn Benediktsson and Bennett, {Amanda J.} and Roza Blagieva and Eric Boerwinkle and Bonnycastle, {Lori L.} and Bostrom, {Kristina Bengtsson} and Bert Bravenboer and Suzannah Bumpstead and Burtt, {Noisel P.} and Guillaume Charpentier and Chines, {Peter S.} and Marilyn Cornelis and Couper, {David J.} and Gabe Crawford and Doney, {Alex S. F.} and Elliott, {Katherine S.} and Elliott, {Amanda L.} and Erdos, {Michael R.} and Fox, {Caroline S.} and Franklin, {Christopher S.} and Martha Ganser and Morris, {Andrew D.} and Palmer, {Colin N. A.} and {GIANT Consortium, MAGIC Investigators}",

year = "2010",

month = jul,

doi = "10.1038/ng.609",

language = "English",

volume = "42",

pages = "579--U155",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "7",

}

Voight, BF, Scott, LJ, Steinthorsdottir, V, Morris, AP, Dina, C, Welch, RP, Zeggini, E, Huth, C, Aulchenko, YS, Thorleifsson, G, McCulloch, LJ, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, CJ, Raychaudhuri, S, McCarroll, SA, Langenberg, C, Hofmann, OM, Dupuis, J, Qi, L, Segre, AV, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, AJ, Blagieva, R, Boerwinkle, E, Bonnycastle, LL, Bostrom, KB, Bravenboer, B, Bumpstead, S, Burtt, NP, Charpentier, G, Chines, PS, Cornelis, M, Couper, DJ, Crawford, G, Doney, ASF, Elliott, KS, Elliott, AL, Erdos, MR, Fox, CS, Franklin, CS, Ganser, M, Morris, AD, Palmer, CNA & GIANT Consortium, MAGIC Investigators 2010, 'Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis', Nature Genetics, vol. 42, no. 7, pp. 579-U155. https://doi.org/10.1038/ng.609

TY - JOUR

T1 - Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

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 J.

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 - Franklin, Christopher S.

AU - Ganser, Martha

AU - Morris, Andrew D.

AU - Palmer, Colin N. A.

AU - GIANT Consortium, MAGIC Investigators

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 - GENOME-WIDE ASSOCIATION

KW - C-REACTIVE PROTEIN

KW - FASTING PLASMA-GLUCOSE

KW - QT INTERVAL DURATION

KW - INSULIN-RESISTANCE

KW - COMMON VARIANTS

KW - COMPLEX DISEASES

KW - GENE-EXPRESSION

KW - HNF1-ALPHA GENE

KW - CROHNS-DISEASE

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 -

Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Abstract

Keywords

UN SDGs

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