Show simple item record

dc.contributor.authorRuth, KSen_US
dc.contributor.authorBennett, CEen_US
dc.contributor.authorSchoemaker, MJen_US
dc.contributor.authorWeedon, MNen_US
dc.contributor.authorSwerdlow, AJen_US
dc.contributor.authorMurray, Aen_US
dc.date.accessioned2016-09-28T09:32:11Z
dc.date.issued2016-10en_US
dc.identifier.citationHuman reproduction (Oxford, England), 2016, 31 (10), pp. 2396 - 2403en_US
dc.identifier.issn0268-1161en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/122
dc.identifier.eissn1460-2350en_US
dc.identifier.doi10.1093/humrep/dew204en_US
dc.description.abstract<h4>Study question</h4>Is the length of FMR1 repeat alleles within the normal range associated with the risk of early menopause?<h4>Summary answer</h4>The length of repeat alleles within the normal range does not substantially affect risk of early menopause.<h4>What is known already</h4>There is a strong, well-established relationship between length of premutation FMR1 alleles and age at menopause, suggesting that this relationship could continue into the normal range. Within the normal range, there is conflicting evidence; differences in ovarian reserve have been identified with FMR1 repeat allele length, but a recent population-based study did not find any association with age at menopause as a quantitative trait.<h4>Study design, size, duration</h4>We analysed cross-sectional baseline survey data collected at recruitment from 2004 to 2010 from a population-based, prospective epidemiological cohort study of >110 000 women to investigate whether repeat allele length was associated with early menopause.<h4>Participants/materials, setting, method</h4>We included 4333 women from the Breakthrough Generations Study (BGS), of whom 2118 were early menopause cases (menopause under 46 years) and 2215 were controls. We analysed the relationship between length of FMR1 alleles and early menopause using logistic regression with allele length as continuous and categorical variables. We also conducted analyses with the outcome age at menopause as a quantitative trait as well as appropriate sensitivity and exploratory analyses.<h4>Main results and the role of chance</h4>There was no association of the shorter or longer FMR1 allele or their combined genotype with the clinically relevant end point of early menopause in our main analysis. Likewise, there were no associations with age at menopause as a quantitative trait in our secondary analysis.<h4>Limitations, reasons for caution</h4>Women with homozygous alleles in the normal range may have undetected FMR1 premutation alleles, although there was no evidence to suggest this. We estimate minor dilution of risk of early menopause from the likely inclusion of some women with menopause at over 45 years in the early menopause cases due to age-rounding bias in self-reports.<h4>Wider implications of the findings</h4>There is no robust evidence in this large study that variation within the normal range of FMR1 repeat alleles influences timing of menopause in the general population, which contradicts findings from some earlier, mainly smaller studies. The FMR1 CGG repeat polymorphism in the normal range is unlikely to contribute to genetic susceptibility to early menopause.<h4>Study funding/competing interests</h4>We thank Breast Cancer Now and The Institute of Cancer Research for funding the BGS. The Institute of Cancer Research acknowledges NHS funding to the NIHR Biomedical Research Centre. The study was funded by the Wellcome Trust (grant number 085943). There are no competing interests.<h4>Trial registration number</h4>Not applicable.en_US
dc.formatPrint-Electronicen_US
dc.format.extent2396 - 2403en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectHumansen_US
dc.subjectMenopause, Prematureen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectCross-Sectional Studiesen_US
dc.subjectTrinucleotide Repeatsen_US
dc.subjectMenopauseen_US
dc.subjectGenotypeen_US
dc.subjectAllelesen_US
dc.subjectAdulten_US
dc.subjectMiddle Ageden_US
dc.subjectFemaleen_US
dc.subjectFragile X Mental Retardation Proteinen_US
dc.subjectGenetic Association Studiesen_US
dc.titleLength of FMR1 repeat alleles within the normal range does not substantially affect the risk of early menopause.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-07-22en_US
rioxxterms.versionofrecord10.1093/humrep/dew204en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2016-10en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfHuman reproduction (Oxford, England)en_US
pubs.issue10en_US
pubs.notesNot knownen_US
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-statusPublisheden_US
pubs.volume31en_US
pubs.embargo.termsNot knownen_US
icr.researchteamAetiological Epidemiologyen_US
dc.contributor.icrauthorSwerdlow, Anthonyen_US
dc.contributor.icrauthorSchoemaker, Minouken_US


Files in this item

Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record