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Genetic variation in GPR133 is associated with height: genome wide association study in the self-contained population of Sorbs

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Author

  • Anke Toenjes
  • Moritz Koriath
  • Dorit Schleinitz
  • Kerstin Dietrich
  • Yvonne Boettcher
  • Nigel W. Rayner
  • Peter Almgren
  • Beate Enigk
  • Olaf Richter
  • Silvio Rohm
  • Antje Fischer-Rosinsky
  • Andreas Pfeiffer
  • Katrin Hoffmann
  • Knut Krohn
  • Gabriela Aust
  • Joachim Spranger
  • Leif Groop
  • Matthias Blueher
  • Peter Kovacs
  • Michael Stumvoll
Show all

Summary, in English

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) (similar to 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.

Publishing year

2009

Language

English

Pages

4662-4668

Publication/Series

Human Molecular Genetics

Volume

18

Issue

23

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Medical Genetics

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 0964-6906