Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 284-290 |
| Number of pages | 7 |
| Journal | European Journal of Human Genetics |
| Volume | 24 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2016 |
Fingerprint
Cite this
}
Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes. / Ruth, K.S.; Campbell, P.J.; Chew, S.; Lim, E.M.; Hadlow, N.; Stuckey, Bronwyn; Brown, S.J.; Feenstra, B.; Joseph, J.; Surdulescu, G.L.; Zheng, H.F.; Richards, J.B.; Murray, A.; Spector, T.D.; Wilson, Scott; Perry, J.R.B.
In: European Journal of Human Genetics, Vol. 24, No. 2, 2016, p. 284-290.Research output: Contribution to journal › Article
TY - JOUR
T1 - Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes
AU - Ruth, K.S.
AU - Campbell, P.J.
AU - Chew, S.
AU - Lim, E.M.
AU - Hadlow, N.
AU - Stuckey, Bronwyn
AU - Brown, S.J.
AU - Feenstra, B.
AU - Joseph, J.
AU - Surdulescu, G.L.
AU - Zheng, H.F.
AU - Richards, J.B.
AU - Murray, A.
AU - Spector, T.D.
AU - Wilson, Scott
AU - Perry, J.R.B.
PY - 2016
Y1 - 2016
N2 - © 2016 Macmillan Publishers Limited All rights reserved. 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<5x10-8), 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.
AB - © 2016 Macmillan Publishers Limited All rights reserved. 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<5x10-8), 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.
U2 - 10.1038/ejhg.2015.102
DO - 10.1038/ejhg.2015.102
M3 - Article
VL - 24
SP - 284
EP - 290
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 2
ER -