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

Toenjes, Anke ; Koriath, Moritz ; Schleinitz, Dorit ; Dietrich, Kerstin ; Boettcher, Yvonne ; Rayner, Nigel W. ; Almgren, Peter LU ; Enigk, Beate ; Richter, Olaf and Rohm, Silvio , et al. (2009) In Human Molecular Genetics 18(23). p.4662-4668
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
18
issue
23
pages
4662 - 4668
publisher
Oxford University Press
external identifiers
  • wos:000271573900018
  • scopus:70449334180
ISSN
0964-6906
DOI
10.1093/hmg/ddp423
language
English
LU publication?
yes
id
e6de07a0-0692-4406-a14f-340d988fcf59 (old id 1520180)
date added to LUP
2016-04-01 11:44:47
date last changed
2024-01-07 18:55:37
@article{e6de07a0-0692-4406-a14f-340d988fcf59,
  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 &lt; 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 &lt; 10(-5) and 455 SNPs with P-value &lt; 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.}},
  author       = {{Toenjes, Anke and Koriath, Moritz and Schleinitz, Dorit and Dietrich, Kerstin and Boettcher, Yvonne and Rayner, Nigel W. and Almgren, Peter and Enigk, Beate and Richter, Olaf and Rohm, Silvio and Fischer-Rosinsky, Antje and Pfeiffer, Andreas and Hoffmann, Katrin and Krohn, Knut and Aust, Gabriela and Spranger, Joachim and Groop, Leif and Blueher, Matthias and Kovacs, Peter and Stumvoll, Michael}},
  issn         = {{0964-6906}},
  language     = {{eng}},
  number       = {{23}},
  pages        = {{4662--4668}},
  publisher    = {{Oxford University Press}},
  series       = {{Human Molecular Genetics}},
  title        = {{Genetic variation in GPR133 is associated with height: genome wide association study in the self-contained population of Sorbs}},
  url          = {{http://dx.doi.org/10.1093/hmg/ddp423}},
  doi          = {{10.1093/hmg/ddp423}},
  volume       = {{18}},
  year         = {{2009}},
}