Human Molecular Genetics Advance Access originally published online on September 3, 2009
Human Molecular Genetics 2009 18(23):4662-4668; doi:10.1093/hmg/ddp423
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Genetic variation in GPR133 is associated with height: genome wide association study in the self-contained population of Sorbs
1 Department of Medicine, 2 Coordination Centre for Clinical Trials, 3 Interdisciplinary Centre for Clinical Research, 4 Department of Surgery, Research Laboratories and Clinic of Visceral, Transplantation, Thoracic, and Vascular Surgery, University of Leipzig, Leipzig, Germany, 5 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK, 6 Department of Clinical Sciences/Diabetes and Endocrinology, Lund University, Malmö, Schweden, 7 Department of Endocrinology, Diabetes and Nutrition, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Nuthetal, Germany, 8 Department of Clinical Nutrition, Berlin and German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany and 9 Institute for Human Genetics, University of Berlin, Charite, Berlin, Germany
* To whom correspondence should be addressed at: Department of Medicine, University of Leipzig, Liebigstr. 18, 04109 Leipzig, Germany. Tel: +49 3419713380; Fax: +49 3419713389; Email: michael.stumvoll{at}medizin.uni-leipzig.de
Received July 20, 2009; Revised August 25, 2009; Accepted August 31, 2009
Recently, associations of several common genetic variants with height have been reported in different populations. We attempted to identify further variants associated with adult height in a self-contained population (the Sorbs in Eastern Germany) as discovery set. We performed a genome wide association study (GWAS) (
390 000 genetic polymorphisms, Affymetrix gene arrays) on adult height in 929 Sorbian individuals. Subsequently, the best SNPs (P < 0.001) were taken forward to a meta-analysis together with two independent cohorts [Diabetes Genetics Initiative, British 1958 Birth Cohort, (58BC, publicly available)]. Furthermore, we genotyped our best signal for replication in two additional German cohorts (Leipzig, n = 1044 and Berlin, n = 1728). In the primary Sorbian GWAS, we identified 5 loci with a P-value < 10–5 and 455 SNPs with P-value < 0.001. In the meta-analysis on those 455 SNPs, only two variants in GPR133 (rs1569019 and rs1976930; in LD with each other) retained a P-value at or below 10–6 and were associated with height in the three cohorts individually. Upon replication, the SNP rs1569019 showed significant effects on height in the Leipzig cohort (P = 0.004, beta = 1.166) and in 577 men of the Berlin cohort (P = 0.049, beta = 1.127) though not in women. The combined analysis of all five cohorts (n = 6,687) resulted in a P-value of 4.7 x 10–8 (beta = 0.949). In conclusion, our GWAS suggests novel loci influencing height. In view of the robust replication in five different cohorts, we propose GPR133 to be a novel gene associated with adult height.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.