title: Extended haplotypes in the growth hormone releasing hormone receptor gene (GHRHR) are associated with normal variation in height.
abstract: Mutations in the gene for growth hormone releasing hormone receptor (GHRHR) cause isolated growth hormone deficiency (IGHD) but this gene has not been found to affect normal variation in height. We performed a whole genome linkage analysis for height in a population from northern Sweden and identified a region on chromosome 7 with a lod-score of 4.7. The GHRHR gene is located in this region and typing of tagSNPs identified a haplotype that is associated with height (p = 0.00077) in the original study population. Analysis of a sample from an independent population from the most northern part of Sweden also showed an association with height (p = 0.0039) but with another haplotype in the GHRHR gene. Both haplotypes span the 3' part of the GHRHR gene, including the region in which most of the mutations in IGHD have been located. The effect size of these haplotypes are larger than that of any gene previously associated with height, which indicates that GHRHR might be one of the most important genes so far identified affecting normal variation in human height.
authors.affiliation: Department of Genetics and Pathology, Rudbeck laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Asa
authors.initials: A
authors.lastname: Johansson
authors.forename: Inger
authors.initials: I
authors.lastname: Jonasson
authors.forename: Ulf
authors.initials: U
authors.lastname: Gyllensten
mesh_terms: D001827:Body Height / Q000235:genetics*; D015331:Cohort Studies; D008040:Genetic Linkage; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; C048250:somatotropin releasing hormone receptor