Genome-Wide Association Analysis of Metabolic Traits
Linear regression models were used for association of phenotypes (z-score residuals of insulin secretion and action traits) with genotypes coded additively. Discovery (stage 1) GWAS analyses were carried out using a statistical tool that was able to account for genotype uncertainty, SNPTEST [29] (link), or by using allele dosages in the linear regression model in MACH2QTL [30] (link), [31] (link), probABEL [32] , corrected for residual inflation of the test statistics using the genomic control method [33] (link). The meta-analyses of effect sizes were performed with the fixed-effect inverse-variance method using GWAMA [34] (link). The GC correction was applied only once to cohort-specific results before including them into the meta-analyses. Sex-differentiated analyses were performed using GWAMA, with an assumed heterogeneity p-value of <0.05. Effect sizes for glucose levels were estimated using a fixed-effect model using the metaphor package for R version 2.14.2 (http://www.r-project.org/).
Prokopenko I., Poon W., Mägi R., Prasad B R., Salehi S.A., Almgren P., Osmark P., Bouatia-Naji N., Wierup N., Fall T., Stančáková A., Barker A., Lagou V., Osmond C., Xie W., Lahti J., Jackson A.U., Cheng Y.C., Liu J., O'Connell J.R., Blomstedt P.A., Fadista J., Alkayyali S., Dayeh T., Ahlqvist E., Taneera J., Lecoeur C., Kumar A., Hansson O., Hansson K., Voight B.F., Kang H.M., Levy-Marchal C., Vatin V., Palotie A., Syvänen A.C., Mari A., Weedon M.N., Loos R.J., Ong K.K., Nilsson P., Isomaa B., Tuomi T., Wareham N.J., Stumvoll M., Widen E., Lakka T.A., Langenberg C., Tönjes A., Rauramaa R., Kuusisto J., Frayling T.M., Froguel P., Walker M., Eriksson J.G., Ling C., Kovacs P., Ingelsson E., McCarthy M.I., Shuldiner A.R., Silver K.D., Laakso M., Groop L, & Lyssenko V. (2014). A Central Role for GRB10 in Regulation of Islet Function in Man. PLoS Genetics, 10(4), e1004235.
Corresponding Organization : Steno Diabetes Center
Other organizations :
Hammersmith Hospital, Imperial College London, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Wellcome Centre for Human Genetics, University of Tartu, Paris Cardiovascular Research Center, Inserm, Université Lille Nord de France, Institut Pasteur de Lille, Centre National de la Recherche Scientifique, Science for Life Laboratory, Uppsala University, University of Eastern Finland, Kuopio University Hospital, MRC Epidemiology Unit, University of Cambridge, MRC Lifecourse Epidemiology Unit, University of Southampton, Peninsula College of Medicine and Dentistry, University of Exeter, Folkhälsans Forskningscentrum, University of Michigan–Ann Arbor, Michigan United, University of Maryland, Baltimore, Åbo Akademi University, Finnish Institute for Health and Welfare, Scania (Sweden), Swiss Tropical and Public Health Institute, University of Basel, University of Pennsylvania, GIS-Institut pour la Recherche en Santé Publique, Hôpital Robert-Debré, Wellcome Sanger Institute, Broad Institute, Massachusetts Institute of Technology, Helsinki University Hospital, Skåne University Hospital, Leipzig University, IFB Adiposity Diseases, Newcastle University, Churchill Hospital, Geriatric Research Education and Clinical Center
Phenotypes (z-score residuals of insulin secretion and action traits)
control variables
Genotype uncertainty was accounted for in the statistical analyses
Residual inflation of the test statistics was corrected using the genomic control method
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