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

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Abstract

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.

Details

Authors
  • 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
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Pages (from-to)4662-4668
JournalHuman Molecular Genetics
Volume18
Issue number23
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes