Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

RA Scott; V Lagou; RP Welch; E Wheeler; ME Montasser; JA Luan; R Magi; RJ Strawbridge; E Rehnberg; S Gustafsson; S Kanoni; LJ Rasmussen-Torvik; L Yengo; C Lecoeur; D Shungin; S Sanna; C Sidore; PCD Johnson; JW Jukema; T Johnson; A Mahajan; N Verweij; G Thorleifsson; JJ (Jouke Jan) Hottenga; S Shah; AV Smith; B Sennblad; C Gieger; P Salo; M Perola; NJ Timpson; DM Evans; B St Pourcain; Fenny Wu; JS Andrews; JN Hui; LF Bielak; W Zhao; M Horikoshi; P Navarro; Aaron Isaacs; JR O'Connell; K Stirrups; V Vitart; C Hayward; T Esko; E Mihailov; RM Fraser; T Fall; BF Voight; S Raychaudhuri; H Chen; CM Lindgren; AP Morris; NW Rayner; N Robertson; D Rybin; CT Liu; JS Beckmann; SM Willems; PS Chines; AU Jackson; HM Kang; HM Stringham; KJ Song; T Tanaka; JF Peden; A Goel; AA Hicks; P An; M Muller-Nurasyid; A Franco-Cereceda; L Folkersen; L Marullo; H Jansen; AJ (A.) Oldehinkel; M Bruinenberg; JS Pankow; EN Kari; NG Forouhi; RJF Loos; S Edkins; TV Varga; G Hallmans; H Oksa; M Antonella; R Nagaraja; S Trompet; I Ford; SJL Bakker; A Kong; M Kumari; B Gigante; Cindy Herder; PB Munroe; M Caulfield; J Antti; M Mangino; K Small; I Miljkovic; YM Liu; M Atalay; W Kiess; AL James; Fernando Rivadeneira; André Uitterlinden; CNA Palmer; ASF Doney; G Willemsen; JH Smit; S Campbell; O Polasek; LL Bonnycastle; S Hercberg; M Dimitriou; JL Bolton; GR Fowkes; P Kovacs; J Lindstrom; T Zemunik; S Bandinelli; SH Wild; HV Basart; W Rathmann; H Grallert; W Maerz; ME Kleber; BO Boehm; A Peters; PP Pramstaller; MA Province; IB Borecki; ND Hastie; I Rudan; H Campbell; H Watkins; M Farrall; M Stumvoll; L Ferrucci; DM Waterworth; RN Bergman; FS Collins; J Tuomilehto; RM Watanabe; EJC de Geus; BW Penninx; Bert Hofman; Ben Oostra; BM Psaty; P Vollenweider; JF Wilson; AF Wright; GK Hovingh; A Metspalu; M Uusitupa; PKE Magnusson; KO Kyvik; J Kaprio; JF Price; GV Dedoussis; P Deloukas; P Meneton; L Lind; M Boehnke; AR Shuldiner; Cornelia Duijn; AD Morris; A Toenjes; PA Peyser; JP Beilby; A Korner; J Kuusisto; M Laakso; SR Bornstein; PEH Schwarz; TA Lakka; R Rauramaa; LS Adair; GD Smith; TD Spector; T Illig; U de Faire; A Hamsten; V Gudnason; M Kivimaki; A Hingorani; SM Keinanen-Kiukaanniemi; TE Saaristo; DI Boomsma; K Stefansson; P van der Harst; J Dupuis; NL Pedersen; N Sattar; TB Harris; F Cucca; S Ripatti; V Salomaa; KL Mohlke; B Balkau; P Froguel; A Pouta; MR Jarvelin; NJ Wareham; N Bouatia-Naji; MI McCarthy; PW Franks; JB Meigs; TM Teslovich; JC Florez; C Langenberg; E Ingelsson; I Prokopenko; I Barroso

doi:10.1038/ng.2385

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

RA Scott, V Lagou, RP Welch, E Wheeler, ME Montasser, JA Luan, R Magi, RJ Strawbridge, E Rehnberg, S Gustafsson, S Kanoni, LJ Rasmussen-Torvik, L Yengo, C Lecoeur, D Shungin, S Sanna, C Sidore, PCD Johnson, JW Jukema, T JohnsonA Mahajan, N Verweij, G Thorleifsson, JJ (Jouke Jan) Hottenga, S Shah, AV Smith, B Sennblad, C Gieger, P Salo, M Perola, NJ Timpson, DM Evans, B St Pourcain, Fenny Wu, JS Andrews, JN Hui, LF Bielak, W Zhao, M Horikoshi, P Navarro, Aaron Isaacs, JR O'Connell, K Stirrups, V Vitart, C Hayward, T Esko, E Mihailov, RM Fraser, T Fall, BF Voight, S Raychaudhuri, H Chen, CM Lindgren, AP Morris, NW Rayner, N Robertson, D Rybin, CT Liu, JS Beckmann, SM Willems, PS Chines, AU Jackson, HM Kang, HM Stringham, KJ Song, T Tanaka, JF Peden, A Goel, AA Hicks, P An, M Muller-Nurasyid, A Franco-Cereceda, L Folkersen, L Marullo, H Jansen, AJ (A.) Oldehinkel, M Bruinenberg, JS Pankow, EN Kari, NG Forouhi, RJF Loos, S Edkins, TV Varga, G Hallmans, H Oksa, M Antonella, R Nagaraja, S Trompet, I Ford, SJL Bakker, A Kong, M Kumari, B Gigante, Cindy Herder, PB Munroe, M Caulfield, J Antti, M Mangino, K Small, I Miljkovic, YM Liu, M Atalay, W Kiess, AL James, Fernando Rivadeneira, André Uitterlinden, CNA Palmer, ASF Doney, G Willemsen, JH Smit, S Campbell, O Polasek, LL Bonnycastle, S Hercberg, M Dimitriou, JL Bolton, GR Fowkes, P Kovacs, J Lindstrom, T Zemunik, S Bandinelli, SH Wild, HV Basart, W Rathmann, H Grallert, W Maerz, ME Kleber, BO Boehm, A Peters, PP Pramstaller, MA Province, IB Borecki, ND Hastie, I Rudan, H Campbell, H Watkins, M Farrall, M Stumvoll, L Ferrucci, DM Waterworth, RN Bergman, FS Collins, J Tuomilehto, RM Watanabe, EJC de Geus, BW Penninx, Bert Hofman, Ben Oostra, BM Psaty, P Vollenweider, JF Wilson, AF Wright, GK Hovingh, A Metspalu, M Uusitupa, PKE Magnusson, KO Kyvik, J Kaprio, JF Price, GV Dedoussis, P Deloukas, P Meneton, L Lind, M Boehnke, AR Shuldiner, Cornelia Duijn, AD Morris, A Toenjes, PA Peyser, JP Beilby, A Korner, J Kuusisto, M Laakso, SR Bornstein, PEH Schwarz, TA Lakka, R Rauramaa, LS Adair, GD Smith, TD Spector, T Illig, U de Faire, A Hamsten, V Gudnason, M Kivimaki, A Hingorani, SM Keinanen-Kiukaanniemi, TE Saaristo, DI Boomsma, K Stefansson, P van der Harst, J Dupuis, NL Pedersen, N Sattar, TB Harris, F Cucca, S Ripatti, V Salomaa, KL Mohlke, B Balkau, P Froguel, A Pouta, MR Jarvelin, NJ Wareham, N Bouatia-Naji, MI McCarthy, PW Franks, JB Meigs, TM Teslovich, JC Florez, C Langenberg, E Ingelsson, I Prokopenko, I Barroso

Research output: Contribution to journal › Article › Academic › peer-review

684 Citations (Scopus)

Abstract

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

Original language	Undefined/Unknown
Pages (from-to)	991-+
Journal	Nature Genetics
Volume	44
Issue number	9
DOIs	https://doi.org/10.1038/ng.2385
Publication status	Published - 2012

Research programs

EMC MGC-02-96-01
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02

UN SDGs

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

Access to Document

10.1038/ng.2385

http://hdl.handle.net/1765/58771

Cite this

Scott, RA., Lagou, V., Welch, RP., Wheeler, E., Montasser, ME., Luan, JA., Magi, R., Strawbridge, RJ., Rehnberg, E., Gustafsson, S., Kanoni, S., Rasmussen-Torvik, LJ., Yengo, L., Lecoeur, C., Shungin, D., Sanna, S., Sidore, C., Johnson, PCD., Jukema, JW., ... Barroso, I. (2012). Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nature Genetics, 44(9), 991-+. https://doi.org/10.1038/ng.2385

@article{3c443567885544e2bbbf1fadc970195a,

title = "Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways",

abstract = "Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.",

author = "RA Scott and V Lagou and RP Welch and E Wheeler and ME Montasser and JA Luan and R Magi and RJ Strawbridge and E Rehnberg and S Gustafsson and S Kanoni and LJ Rasmussen-Torvik and L Yengo and C Lecoeur and D Shungin and S Sanna and C Sidore and PCD Johnson and JW Jukema and T Johnson and A Mahajan and N Verweij and G Thorleifsson and Hottenga, {JJ (Jouke Jan)} and S Shah and AV Smith and B Sennblad and C Gieger and P Salo and M Perola and NJ Timpson and DM Evans and {St Pourcain}, B and Fenny Wu and JS Andrews and JN Hui and LF Bielak and W Zhao and M Horikoshi and P Navarro and Aaron Isaacs and JR O'Connell and K Stirrups and V Vitart and C Hayward and T Esko and E Mihailov and RM Fraser and T Fall and BF Voight and S Raychaudhuri and H Chen and CM Lindgren and AP Morris and NW Rayner and N Robertson and D Rybin and CT Liu and JS Beckmann and SM Willems and PS Chines and AU Jackson and HM Kang and HM Stringham and KJ Song and T Tanaka and JF Peden and A Goel and AA Hicks and P An and M Muller-Nurasyid and A Franco-Cereceda and L Folkersen and L Marullo and H Jansen and Oldehinkel, {AJ (A.)} and M Bruinenberg and JS Pankow and EN Kari and NG Forouhi and RJF Loos and S Edkins and TV Varga and G Hallmans and H Oksa and M Antonella and R Nagaraja and S Trompet and I Ford and SJL Bakker and A Kong and M Kumari and B Gigante and Cindy Herder and PB Munroe and M Caulfield and J Antti and M Mangino and K Small and I Miljkovic and YM Liu and M Atalay and W Kiess and AL James and Fernando Rivadeneira and Andr{\'e} Uitterlinden and CNA Palmer and ASF Doney and G Willemsen and JH Smit and S Campbell and O Polasek and LL Bonnycastle and S Hercberg and M Dimitriou and JL Bolton and GR Fowkes and P Kovacs and J Lindstrom and T Zemunik and S Bandinelli and SH Wild and HV Basart and W Rathmann and H Grallert and W Maerz and ME Kleber and BO Boehm and A Peters and PP Pramstaller and MA Province and IB Borecki and ND Hastie and I Rudan and H Campbell and H Watkins and M Farrall and M Stumvoll and L Ferrucci and DM Waterworth and RN Bergman and FS Collins and J Tuomilehto and RM Watanabe and {de Geus}, EJC and BW Penninx and Bert Hofman and Ben Oostra and BM Psaty and P Vollenweider and JF Wilson and AF Wright and GK Hovingh and A Metspalu and M Uusitupa and PKE Magnusson and KO Kyvik and J Kaprio and JF Price and GV Dedoussis and P Deloukas and P Meneton and L Lind and M Boehnke and AR Shuldiner and Cornelia Duijn and AD Morris and A Toenjes and PA Peyser and JP Beilby and A Korner and J Kuusisto and M Laakso and SR Bornstein and PEH Schwarz and TA Lakka and R Rauramaa and LS Adair and GD Smith and TD Spector and T Illig and {de Faire}, U and A Hamsten and V Gudnason and M Kivimaki and A Hingorani and SM Keinanen-Kiukaanniemi and TE Saaristo and DI Boomsma and K Stefansson and {van der Harst}, P and J Dupuis and NL Pedersen and N Sattar and TB Harris and F Cucca and S Ripatti and V Salomaa and KL Mohlke and B Balkau and P Froguel and A Pouta and MR Jarvelin and NJ Wareham and N Bouatia-Naji and MI McCarthy and PW Franks and JB Meigs and TM Teslovich and JC Florez and C Langenberg and E Ingelsson and I Prokopenko and I Barroso",

year = "2012",

doi = "10.1038/ng.2385",

language = "Undefined/Unknown",

volume = "44",

pages = "991--+",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "9",

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Scott, RA, Lagou, V, Welch, RP, Wheeler, E, Montasser, ME, Luan, JA, Magi, R, Strawbridge, RJ, Rehnberg, E, Gustafsson, S, Kanoni, S, Rasmussen-Torvik, LJ, Yengo, L, Lecoeur, C, Shungin, D, Sanna, S, Sidore, C, Johnson, PCD, Jukema, JW, Johnson, T, Mahajan, A, Verweij, N, Thorleifsson, G, Hottenga, JJ, Shah, S, Smith, AV, Sennblad, B, Gieger, C, Salo, P, Perola, M, Timpson, NJ, Evans, DM, St Pourcain, B, Wu, F, Andrews, JS, Hui, JN, Bielak, LF, Zhao, W, Horikoshi, M, Navarro, P, Isaacs, A, O'Connell, JR, Stirrups, K, Vitart, V, Hayward, C, Esko, T, Mihailov, E, Fraser, RM, Fall, T, Voight, BF, Raychaudhuri, S, Chen, H, Lindgren, CM, Morris, AP, Rayner, NW, Robertson, N, Rybin, D, Liu, CT, Beckmann, JS, Willems, SM, Chines, PS, Jackson, AU, Kang, HM, Stringham, HM, Song, KJ, Tanaka, T, Peden, JF, Goel, A, Hicks, AA, An, P, Muller-Nurasyid, M, Franco-Cereceda, A, Folkersen, L, Marullo, L, Jansen, H, Oldehinkel, AJ, Bruinenberg, M, Pankow, JS, Kari, EN, Forouhi, NG, Loos, RJF, Edkins, S, Varga, TV, Hallmans, G, Oksa, H, Antonella, M, Nagaraja, R, Trompet, S, Ford, I, Bakker, SJL, Kong, A, Kumari, M, Gigante, B, Herder, C, Munroe, PB, Caulfield, M, Antti, J, Mangino, M, Small, K, Miljkovic, I, Liu, YM, Atalay, M, Kiess, W, James, AL, Rivadeneira, F , Uitterlinden, A, Palmer, CNA, Doney, ASF, Willemsen, G, Smit, JH, Campbell, S, Polasek, O, Bonnycastle, LL, Hercberg, S, Dimitriou, M, Bolton, JL, Fowkes, GR, Kovacs, P, Lindstrom, J, Zemunik, T, Bandinelli, S, Wild, SH, Basart, HV, Rathmann, W, Grallert, H, Maerz, W, Kleber, ME, Boehm, BO, Peters, A, Pramstaller, PP, Province, MA, Borecki, IB, Hastie, ND, Rudan, I, Campbell, H, Watkins, H, Farrall, M, Stumvoll, M, Ferrucci, L, Waterworth, DM, Bergman, RN, Collins, FS, Tuomilehto, J, Watanabe, RM, de Geus, EJC, Penninx, BW, Hofman, B, Oostra, B, Psaty, BM, Vollenweider, P, Wilson, JF, Wright, AF, Hovingh, GK, Metspalu, A, Uusitupa, M, Magnusson, PKE, Kyvik, KO, Kaprio, J, Price, JF, Dedoussis, GV, Deloukas, P, Meneton, P, Lind, L, Boehnke, M, Shuldiner, AR, Duijn, C, Morris, AD, Toenjes, A, Peyser, PA, Beilby, JP, Korner, A, Kuusisto, J, Laakso, M, Bornstein, SR, Schwarz, PEH, Lakka, TA, Rauramaa, R, Adair, LS, Smith, GD, Spector, TD, Illig, T, de Faire, U, Hamsten, A, Gudnason, V, Kivimaki, M, Hingorani, A, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Boomsma, DI, Stefansson, K, van der Harst, P, Dupuis, J, Pedersen, NL, Sattar, N, Harris, TB, Cucca, F, Ripatti, S, Salomaa, V, Mohlke, KL, Balkau, B, Froguel, P, Pouta, A, Jarvelin, MR, Wareham, NJ, Bouatia-Naji, N, McCarthy, MI, Franks, PW, Meigs, JB, Teslovich, TM, Florez, JC, Langenberg, C, Ingelsson, E, Prokopenko, I & Barroso, I 2012, 'Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways', Nature Genetics, vol. 44, no. 9, pp. 991-+. https://doi.org/10.1038/ng.2385

TY - JOUR

T1 - Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

AU - Scott, RA

AU - Lagou, V

AU - Welch, RP

AU - Wheeler, E

AU - Montasser, ME

AU - Luan, JA

AU - Magi, R

AU - Strawbridge, RJ

AU - Rehnberg, E

AU - Gustafsson, S

AU - Kanoni, S

AU - Rasmussen-Torvik, LJ

AU - Yengo, L

AU - Lecoeur, C

AU - Shungin, D

AU - Sanna, S

AU - Sidore, C

AU - Johnson, PCD

AU - Jukema, JW

AU - Johnson, T

AU - Mahajan, A

AU - Verweij, N

AU - Thorleifsson, G

AU - Hottenga, JJ (Jouke Jan)

AU - Shah, S

AU - Smith, AV

AU - Sennblad, B

AU - Gieger, C

AU - Salo, P

AU - Perola, M

AU - Timpson, NJ

AU - Evans, DM

AU - St Pourcain, B

AU - Wu, Fenny

AU - Andrews, JS

AU - Hui, JN

AU - Bielak, LF

AU - Zhao, W

AU - Horikoshi, M

AU - Navarro, P

AU - Isaacs, Aaron

AU - O'Connell, JR

AU - Stirrups, K

AU - Vitart, V

AU - Hayward, C

AU - Esko, T

AU - Mihailov, E

AU - Fraser, RM

AU - Fall, T

AU - Voight, BF

AU - Raychaudhuri, S

AU - Chen, H

AU - Lindgren, CM

AU - Morris, AP

AU - Rayner, NW

AU - Robertson, N

AU - Rybin, D

AU - Liu, CT

AU - Beckmann, JS

AU - Willems, SM

AU - Chines, PS

AU - Jackson, AU

AU - Kang, HM

AU - Stringham, HM

AU - Song, KJ

AU - Tanaka, T

AU - Peden, JF

AU - Goel, A

AU - Hicks, AA

AU - An, P

AU - Muller-Nurasyid, M

AU - Franco-Cereceda, A

AU - Folkersen, L

AU - Marullo, L

AU - Jansen, H

AU - Oldehinkel, AJ (A.)

AU - Bruinenberg, M

AU - Pankow, JS

AU - Kari, EN

AU - Forouhi, NG

AU - Loos, RJF

AU - Edkins, S

AU - Varga, TV

AU - Hallmans, G

AU - Oksa, H

AU - Antonella, M

AU - Nagaraja, R

AU - Trompet, S

AU - Ford, I

AU - Bakker, SJL

AU - Kong, A

AU - Kumari, M

AU - Gigante, B

AU - Herder, Cindy

AU - Munroe, PB

AU - Caulfield, M

AU - Antti, J

AU - Mangino, M

AU - Small, K

AU - Miljkovic, I

AU - Liu, YM

AU - Atalay, M

AU - Kiess, W

AU - James, AL

AU - Rivadeneira, Fernando

AU - Uitterlinden, André

AU - Palmer, CNA

AU - Doney, ASF

AU - Willemsen, G

AU - Smit, JH

AU - Campbell, S

AU - Polasek, O

AU - Bonnycastle, LL

AU - Hercberg, S

AU - Dimitriou, M

AU - Bolton, JL

AU - Fowkes, GR

AU - Kovacs, P

AU - Lindstrom, J

AU - Zemunik, T

AU - Bandinelli, S

AU - Wild, SH

AU - Basart, HV

AU - Rathmann, W

AU - Grallert, H

AU - Maerz, W

AU - Kleber, ME

AU - Boehm, BO

AU - Peters, A

AU - Pramstaller, PP

AU - Province, MA

AU - Borecki, IB

AU - Hastie, ND

AU - Rudan, I

AU - Campbell, H

AU - Watkins, H

AU - Farrall, M

AU - Stumvoll, M

AU - Ferrucci, L

AU - Waterworth, DM

AU - Bergman, RN

AU - Collins, FS

AU - Tuomilehto, J

AU - Watanabe, RM

AU - de Geus, EJC

AU - Penninx, BW

AU - Hofman, Bert

AU - Oostra, Ben

AU - Psaty, BM

AU - Vollenweider, P

AU - Wilson, JF

AU - Wright, AF

AU - Hovingh, GK

AU - Metspalu, A

AU - Uusitupa, M

AU - Magnusson, PKE

AU - Kyvik, KO

AU - Kaprio, J

AU - Price, JF

AU - Dedoussis, GV

AU - Deloukas, P

AU - Meneton, P

AU - Lind, L

AU - Boehnke, M

AU - Shuldiner, AR

AU - Duijn, Cornelia

AU - Morris, AD

AU - Toenjes, A

AU - Peyser, PA

AU - Beilby, JP

AU - Korner, A

AU - Kuusisto, J

AU - Laakso, M

AU - Bornstein, SR

AU - Schwarz, PEH

AU - Lakka, TA

AU - Rauramaa, R

AU - Adair, LS

AU - Smith, GD

AU - Spector, TD

AU - Illig, T

AU - de Faire, U

AU - Hamsten, A

AU - Gudnason, V

AU - Kivimaki, M

AU - Hingorani, A

AU - Keinanen-Kiukaanniemi, SM

AU - Saaristo, TE

AU - Boomsma, DI

AU - Stefansson, K

AU - van der Harst, P

AU - Dupuis, J

AU - Pedersen, NL

AU - Sattar, N

AU - Harris, TB

AU - Cucca, F

AU - Ripatti, S

AU - Salomaa, V

AU - Mohlke, KL

AU - Balkau, B

AU - Froguel, P

AU - Pouta, A

AU - Jarvelin, MR

AU - Wareham, NJ

AU - Bouatia-Naji, N

AU - McCarthy, MI

AU - Franks, PW

AU - Meigs, JB

AU - Teslovich, TM

AU - Florez, JC

AU - Langenberg, C

AU - Ingelsson, E

AU - Prokopenko, I

AU - Barroso, I

PY - 2012

Y1 - 2012

N2 - Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

AB - Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

U2 - 10.1038/ng.2385

DO - 10.1038/ng.2385

M3 - Article

SN - 1061-4036

VL - 44

SP - 991-+

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -