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dc.contributor.authorRuth, KS
dc.contributor.authorSoares, ALG
dc.contributor.authorBorges, M-C
dc.contributor.authorEliassen, AH
dc.contributor.authorHankinson, SE
dc.contributor.authorJones, ME
dc.contributor.authorKraft, P
dc.contributor.authorNichols, HB
dc.contributor.authorSandler, DP
dc.contributor.authorSchoemaker, MJ
dc.contributor.authorTaylor, JA
dc.contributor.authorZeleniuch-Jacquotte, A
dc.contributor.authorLawlor, DA
dc.contributor.authorSwerdlow, AJ
dc.contributor.authorMurray, A
dc.date.accessioned2019-01-29T10:30:08Z
dc.date.issued2019-04
dc.identifier.citationHuman molecular genetics, 2019, 28 (8), pp. 1392 - 1401
dc.identifier.issn0964-6906
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3031
dc.identifier.eissn1460-2083
dc.identifier.doi10.1093/hmg/ddz015
dc.description.abstractAnti-Müllerian hormone (AMH) is required for sexual differentiation in the fetus, and in adult females AMH is produced by growing ovarian follicles. Consequently, AMH levels are correlated with ovarian reserve, declining towards menopause when the oocyte pool is exhausted. A previous genome-wide association study identified three genetic variants in and around the AMH gene that explained 25% of variation in AMH levels in adolescent males but did not identify any genetic associations reaching genome-wide significance in adolescent females. To explore the role of genetic variation in determining AMH levels in women of late reproductive age, we carried out a genome-wide meta-analysis in 3344 pre-menopausal women from five cohorts (median age 44-48 years at blood draw). A single genetic variant, rs16991615, previously associated with age at menopause, reached genome-wide significance at P = 3.48 × 10-10, with a per allele difference in age-adjusted inverse normal AMH of 0.26 standard deviations (SD) (95% confidence interval (CI) [0.18,0.34]). We investigated whether genetic determinants of female reproductive lifespan were more generally associated with pre-menopausal AMH levels. Genetically-predicted age at menarche had no robust association but genetically-predicted age at menopause was associated with lower AMH levels by 0.18 SD (95% CI [0.14,0.21]) in age-adjusted inverse normal AMH per one-year earlier age at menopause. Our findings provide genetic support for the well-established use of AMH as a marker of ovarian reserve.
dc.formatPrint
dc.format.extent1392 - 1401
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectOvary
dc.subjectOvarian Follicle
dc.subjectMitochondria
dc.subjectHumans
dc.subjectSequence Analysis, DNA
dc.subjectAge Factors
dc.subjectGene Expression
dc.subjectGene Expression Regulation
dc.subjectBase Sequence
dc.subjectLongevity
dc.subjectReproduction
dc.subjectPremenopause
dc.subjectMenarche
dc.subjectHaplotypes
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectAnti-Mullerian Hormone
dc.subjectGenetic Variation
dc.subjectGenome-Wide Association Study
dc.subjectGenetic Association Studies
dc.subjectTranscriptome
dc.titleGenome-wide association study of anti-Müllerian hormone levels in pre-menopausal women of late reproductive age and relationship with genetic determinants of reproductive lifespan.
dc.typeJournal Article
dcterms.dateAccepted2019-01-10
rioxxterms.versionofrecord10.1093/hmg/ddz015
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2019-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfHuman molecular genetics
pubs.issue8
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology
pubs.publication-statusPublished
pubs.volume28
pubs.embargo.termsNot known
icr.researchteamAetiological Epidemiologyen_US
dc.contributor.icrauthorSwerdlow, Anthonyen
dc.contributor.icrauthorSchoemaker, Minouken
dc.contributor.icrauthorJones, Michaelen


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