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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Bibliographic Details
Published in:European journal of human genetics : EJHG Vol. 24; no. 2; pp. 284 - 290
Main Authors: 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
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.02.2016
Subjects:
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
Online Access:Get full text
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Summary: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.
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These authors contributed equally to this work.
ISSN:1018-4813
1476-5438
1476-5438
DOI:10.1038/ejhg.2015.102