Genetic variation in GPR133 is associated with height: genome wide association study in the self-contained population of Sorbs.
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) (approximately 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.
Tönjes
Anke
A
Department of Medicine, University of Leipzig, Leipzig,Germany.
Koriath
Moritz
M
Schleinitz
Dorit
D
Dietrich
Kerstin
K
Böttcher
Yvonne
Y
Rayner
Nigel W
NW
Almgren
Peter
P
Enigk
Beate
B
Richter
Olaf
O
Rohm
Silvio
S
Fischer-Rosinsky
Antje
A
Pfeiffer
Andreas
A
Hoffmann
Katrin
K
Krohn
Knut
K
Aust
Gabriela
G
Spranger
Joachim
J
Groop
Leif
L
Blüher
Matthias
M
Kovacs
Peter
P
Stumvoll
Michael
M
D000328:Adult; D000368:Aged; D001827:Body Height; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005858:Germany / Q000208:ethnology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D044465:White People / Q000208:ethnology / Q000235:genetics*
C547021:ADGRD1 protein, human; D043562:Receptors, G-Protein-Coupled