@article{1a7fda757ec7428bb4b844d2fc94126d,
title = "A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance",
abstract = "Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.",
keywords = "Blood Glucose/metabolism, Body Mass Index, Cholesterol, HDL/metabolism, Diabetes Mellitus, Type 2/genetics, Genome-Wide Association Study, Humans, Insulin/metabolism, Insulin Resistance/genetics, Polymorphism, Single Nucleotide",
author = "Manning, {Alisa K} and Marie-France Hivert and Scott, {Robert A} and Grimsby, {Jonna L} and Nabila Bouatia-Naji and Han Chen and Denis Rybin and Ching-Ti Liu and Bielak, {Lawrence F} and Inga Prokopenko and Najaf Amin and Daniel Barnes and Gemma Cadby and Jouke-Jan Hottenga and Erik Ingelsson and Jackson, {Anne U} and Toby Johnson and Stavroula Kanoni and Claes Ladenvall and Vasiliki Lagou and Jari Lahti and Cecile Lecoeur and Yongmei Liu and Martinez-Larrad, {Maria Teresa} and Montasser, {May E} and Pau Navarro and Perry, {John R B} and Rasmussen-Torvik, {Laura J} and Perttu Salo and Naveed Sattar and Dmitry Shungin and Strawbridge, {Rona J} and Toshiko Tanaka and {van Duijn}, {Cornelia M} and Ping An and {de Andrade}, Mariza and Andrews, {Jeanette S} and Thor Aspelund and Mustafa Atalay and Yurii Aulchenko and Beverley Balkau and Stefania Bandinelli and Beckmann, {Jacques S} and Beilby, {John P} and Claire Bellis and Bergman, {Richard N} and John Blangero and Mladen Boban and Michael Boehnke and Peter Schwarz and {DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium}",
year = "2012",
month = may,
day = "13",
doi = "10.1038/ng.2274",
language = "English",
volume = "44",
pages = "659--69",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "6",
}