TY - JOUR

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

AU - Scott, Robert A

AU - Lagou, Vasiliki

AU - Welch, Ryan P

AU - Wheeler, Eleanor

AU - Montasser, May E

AU - Luan, Jian'an

AU - Mägi, Reedik

AU - Strawbridge, Rona J

AU - Rehnberg, Emil

AU - Gustafsson, Stefan

AU - Kanoni, Stavroula

AU - Rasmussen-Torvik, Laura J

AU - Yengo, Loïc

AU - Lecoeur, Cecile

AU - Shungin, Dmitry

AU - Sanna, Serena

AU - Sidore, Carlo

AU - Johnson, Paul C D

AU - Jukema, J Wouter

AU - Johnson, Toby

AU - Mahajan, Anubha

AU - Verweij, Niek

AU - Thorleifsson, Gudmar

AU - Hottenga, Jouke-Jan

AU - Shah, Sonia

AU - Smith, Albert V

AU - Sennblad, Bengt

AU - Gieger, Christian

AU - Salo, Perttu

AU - Perola, Markus

AU - Timpson, Nicholas J

AU - Evans, David M

AU - Pourcain, Beate St

AU - Wu, Ying

AU - Andrews, Jeanette S

AU - Hui, Jennie

AU - Bielak, Lawrence F

AU - Zhao, Wei

AU - Horikoshi, Momoko

AU - Navarro, Pau

AU - Isaacs, Aaron

AU - O'Connell, Jeffrey R

AU - Stirrups, Kathleen

AU - Folkersen, Lasse

AU - Loos, Ruth J F

AU - Varga, Tibor V

AU - Kovacs, Peter

AU - Kyvik, Kirsten O

AU - Lind, Lars

AU - Schwarz, Peter E H

AU - Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium

PY - 2012/9

Y1 - 2012/9

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.

KW - Adult

KW - Animals

KW - Blood Glucose/genetics

KW - Fasting/blood

KW - Female

KW - Gene Frequency

KW - Genome-Wide Association Study/statistics & numerical data

KW - Humans

KW - Insulin/blood

KW - Male

KW - Metabolic Networks and Pathways/genetics

KW - Mice

KW - Osmolar Concentration

KW - Quantitative Trait Loci/physiology

U2 - 10.1038/ng.2385

DO - 10.1038/ng.2385

M3 - Journal article

C2 - 22885924

VL - 44

SP - 991

EP - 1005

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 9

ER -