caa a22 4500 445861940 CHVBK 20180317145446.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s00439-010-0917-1 doi (NATIONALLICENCE)springer-10.1007/s00439-010-0917-1 Genetic risk sum score comprised of common polygenic variation is associated with body mass index [Elektronische Daten] [Roseann Peterson, Hermine Maes, Peter Holmans, Alan Sanders, Douglas Levinson, Jianxin Shi, Kenneth Kendler, Pablo Gejman, Bradley Webb] Genome-wide association studies (GWAS) of body mass index (BMI) using large samples have yielded approximately a dozen robustly associated variants and implicated additional loci. Individually these variants have small effects and in aggregate explain a small proportion of the variance. As a result, replication attempts have limited power to achieve genome-wide significance, even with several thousand subjects. Since there is strong prior evidence for genetic influence on BMI for specific variants, alternative approaches to replication can be applied. Instead of testing individual loci sequentially, a genetic risk sum score (GRSS) summarizing the total number of risk alleles can be tested. In the current study, GRSS comprising 56 top variants catalogued from two large meta-analyses was tested for association with BMI in the Molecular Genetics of Schizophrenia controls (2,653 European-Americans, 973 African-Americans). After accounting for covariates known to influence BMI (ancestry, sex, age), GRSS was highly associated with BMI (p value=3.19E−06) although explained a limited amount of the variance (0.66%). However, area under receiver operator criteria curve (AUC) estimates indicated that the GRSS and covariates significantly predicted overweight and obesity classification with maximum discriminative ability for predicting class III obesity (AUC=0.697). The relative contributions of the individual loci to GRSS were examined post hoc and the results were not due to a few highly significant variants, but rather the result of numerous variants of small effect. This study provides evidence of the utility of a GRSS as an alternative approach to replication of common polygenic variation in complex traits. Springer-Verlag, 2010 Peterson Roseann Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Biotech I, 800 E. Leigh Street, 23298-0126, Richmond, VA, USA aut Maes Hermine Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Biotech I, 800 E. Leigh Street, 23298-0126, Richmond, VA, USA aut Holmans Peter Department of Psychological Medicine and Neurology, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK aut Sanders Alan Department of Psychiatry and Behavioral Sciences, Center for Psychiatric Genetics, NorthShore University HealthSystem, Evanston, IL, USA aut Levinson Douglas Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA aut Shi Jianxin Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA aut Kendler Kenneth Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Biotech I, 800 E. Leigh Street, 23298-0126, Richmond, VA, USA aut Gejman Pablo Department of Psychiatry and Behavioral Sciences, Center for Psychiatric Genetics, NorthShore University HealthSystem, Evanston, IL, USA aut Webb Bradley Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Biotech I, 800 E. Leigh Street, 23298-0126, Richmond, VA, USA aut Human Genetics Springer-Verlag 129/2(2011-02-01), 221-230 0340-6717 129:2<221 2011 129 439 https://doi.org/10.1007/s00439-010-0917-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-010-0917-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Peterson Roseann Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Biotech I, 800 E. Leigh Street, 23298-0126, Richmond, VA, USA aut NATIONALLICENCE 700 1- Maes Hermine Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Biotech I, 800 E. Leigh Street, 23298-0126, Richmond, VA, USA aut NATIONALLICENCE 700 1- Holmans Peter Department of Psychological Medicine and Neurology, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK aut NATIONALLICENCE 700 1- Sanders Alan Department of Psychiatry and Behavioral Sciences, Center for Psychiatric Genetics, NorthShore University HealthSystem, Evanston, IL, USA aut NATIONALLICENCE 700 1- Levinson Douglas Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA aut NATIONALLICENCE 700 1- Shi Jianxin Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Kendler Kenneth Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Biotech I, 800 E. Leigh Street, 23298-0126, Richmond, VA, USA aut NATIONALLICENCE 700 1- Gejman Pablo Department of Psychiatry and Behavioral Sciences, Center for Psychiatric Genetics, NorthShore University HealthSystem, Evanston, IL, USA aut NATIONALLICENCE 700 1- Webb Bradley Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Biotech I, 800 E. Leigh Street, 23298-0126, Richmond, VA, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/2(2011-02-01), 221-230 0340-6717 129:2<221 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer