Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes

Genetic factors contribute strongly to sex hormone levels, yet knowledge of the regulatory mechanisms remains incomplete. Genome-wide association studies (GWAS) have identified only a small number of loci associated with sex hormone levels, with several reproductive hormones yet to be assessed. The...

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Vydáno v:	European journal of human genetics : EJHG Ročník 24; číslo 2; s. 284 - 290
Hlavní autoři:	Ruth, Katherine S, Campbell, Purdey J, Chew, Shelby, Lim, Ee Mun, Hadlow, Narelle, Stuckey, Bronwyn GA, Brown, Suzanne J, Feenstra, Bjarke, Joseph, John, Surdulescu, Gabriela L, Zheng, Hou Feng, Richards, J Brent, Murray, Anna, Spector, Tim D, Wilson, Scott G, Perry, John RB
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Nature Publishing Group 01.02.2016
Témata:	Chromosome 7 Dehydroepiandrosterone Dehydroepiandrosterone Sulfate - metabolism Diabetes Epidemiology Estradiol - genetics Female Follicle Stimulating Hormone - genetics Follicle Stimulating Hormone - metabolism Follicle-stimulating hormone Gene expression Gene frequency Genetic factors Genetic variance Genetics Genome, Human Genome-Wide Association Study Genomes Genotype Genotypes Globulins Gonadal Steroid Hormones - genetics Gonadal Steroid Hormones - metabolism Hospitals Humans Kinases Licenses Luteinizing hormone Luteinizing Hormone - genetics Luteinizing Hormone - metabolism Male Males Menstrual cycle Menstruation Metabolism Phenotype Phenotypes Polymorphism, Single Nucleotide - genetics Progesterone Progesterone - genetics Prolactin Prolactin - genetics Prolactin - metabolism Sex Sex Hormone-Binding Globulin - genetics Sex Hormone-Binding Globulin - metabolism Sex hormones Single-nucleotide polymorphism Studies Testosterone Testosterone - genetics Canada Montreal Quebec Canada United Kingdom > UK Australia
ISSN:	1018-4813, 1476-5438, 1476-5438
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Popis
Shrnutí:	Genetic factors contribute strongly to sex hormone levels, yet knowledge of the regulatory mechanisms remains incomplete. Genome-wide association studies (GWAS) have identified only a small number of loci associated with sex hormone levels, with several reproductive hormones yet to be assessed. The aim of the study was to identify novel genetic variants contributing to the regulation of sex hormones. We performed GWAS using genotypes imputed from the 1000 Genomes reference panel. The study used genotype and phenotype data from a UK twin register. We included 2913 individuals (up to 294 males) from the Twins UK study, excluding individuals receiving hormone treatment. Phenotypes were standardised for age, sex, BMI, stage of menstrual cycle and menopausal status. We tested 7,879,351 autosomal SNPs for association with levels of dehydroepiandrosterone sulphate (DHEAS), oestradiol, free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, progesterone, sex hormone-binding globulin and testosterone. Eight independent genetic variants reached genome-wide significance (P<5 × 10(-8)), with minor allele frequencies of 1.3-23.9%. Novel signals included variants for progesterone (P=7.68 × 10(-12)), oestradiol (P=1.63 × 10(-8)) and FAI (P=1.50 × 10(-8)). A genetic variant near the FSHB gene was identified which influenced both FSH (P=1.74 × 10(-8)) and LH (P=3.94 × 10(-9)) levels. A separate locus on chromosome 7 was associated with both DHEAS (P=1.82 × 10(-14)) and progesterone (P=6.09 × 10(-14)). This study highlights loci that are relevant to reproductive function and suggests overlap in the genetic basis of hormone regulation.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work.
ISSN:	1018-4813 1476-5438 1476-5438
DOI:	10.1038/ejhg.2015.102