Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Details

Serval ID
serval:BIB_CFE58C5B5334
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Understanding the genetic complexity of puberty timing across the allele frequency spectrum.
Journal
Nature genetics
Author(s)
Kentistou K.A., Kaisinger L.R., Stankovic S., Vaudel M., Mendes de Oliveira E., Messina A., Walters R.G., Liu X., Busch A.S., Helgason H., Thompson D.J., Santoni F., Petricek K.M., Zouaghi Y., Huang-Doran I., Gudbjartsson D.F., Bratland E., Lin K., Gardner E.J., Zhao Y., Jia R.Y., Terao C., Riggan M.J., Bolla M.K., Yazdanpanah M., Yazdanpanah N., Bradfield J.P., Broer L., Campbell A., Chasman D.I., Cousminer D.L., Franceschini N., Franke L.H., Girotto G., He C., Järvelin M.R., Joshi P.K., Kamatani Y., Karlsson R., Luan J., Lunetta K.L., Mägi R., Mangino M., Medland S.E., Meisinger C., Noordam R., Nutile T., Concas M.P., Polašek O., Porcu E., Ring S.M., Sala C., Smith A.V., Tanaka T., van der Most P.J., Vitart V., Wang C.A., Willemsen G., Zygmunt M., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antoniou A.C., Auer P.L., Barnes CLK, Beckmann M.W., Berrington de Gonzalez A., Bogdanova N.V., Bojesen S.E., Brenner H., Buring J.E., Canzian F., Chang-Claude J., Couch F.J., Cox A., Crisponi L., Czene K., Daly M.B., Demerath E.W., Dennis J., Devilee P., De Vivo I., Dörk T., Dunning A.M., Dwek M., Eriksson J.G., Fasching P.A., Fernandez-Rhodes L., Ferreli L., Fletcher O., Gago-Dominguez M., García-Closas M., García-Sáenz J.A., González-Neira A., Grallert H., Guénel P., Haiman C.A., Hall P., Hamann U., Hakonarson H., Hart R.J., Hickey M., Hooning M.J., Hoppe R., Hopper J.L., Hottenga J.J., Hu F.B., Huebner H., Hunter D.J., Jernström H., John E.M., Karasik D., Khusnutdinova E.K., Kristensen V.N., Lacey J.V., Lambrechts D., Launer L.J., Lind P.A., Lindblom A., Magnusson PKE, Mannermaa A., McCarthy M.I., Meitinger T., Menni C., Michailidou K., Millwood I.Y., Milne R.L., Montgomery G.W., Nevanlinna H., Nolte I.M., Nyholt D.R., Obi N., O'Brien K.M., Offit K., Oldehinkel A.J., Ostrowski S.R., Palotie A., Pedersen O.B., Peters A., Pianigiani G., Plaseska-Karanfilska D., Pouta A., Pozarickij A., Radice P., Rennert G., Rosendaal F.R., Ruggiero D., Saloustros E., Sandler D.P., Schipf S., Schmidt C.O., Schmidt M.K., Small K., Spedicati B., Stampfer M., Stone J., Tamimi R.M., Teras L.R., Tikkanen E., Turman C., Vachon C.M., Wang Q., Winqvist R., Wolk A., Zemel B.S., Zheng W., van Dijk K.W., Alizadeh B.Z., Bandinelli S., Boerwinkle E., Boomsma D.I., Ciullo M., Chenevix-Trench G., Cucca F., Esko T., Gieger C., Grant SFA, Gudnason V., Hayward C., Kolčić I., Kraft P., Lawlor D.A., Martin N.G., Nøhr E.A., Pedersen N.L., Pennell C.E., Ridker P.M., Robino A., Snieder H., Sovio U., Spector T.D., Stöckl D., Sudlow C., Timpson N.J., Toniolo D., Uitterlinden A., Ulivi S., Völzke H., Wareham N.J., Widen E., Wilson J.F., Pharoah PDP, Li L., Easton D.F., Njølstad P.R., Sulem P., Murabito J.M., Murray A., Manousaki D., Juul A., Erikstrup C., Stefansson K., Horikoshi M., Chen Z., Farooqi I.S., Pitteloud N., Johansson S., Day F.R., Perry JRB, Ong K.K.
Working group(s)
ABCTB Investigators, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group
Contributor(s)
John E.M., Hall P., Winqvis R.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
07/2024
Peer-reviewed
Oui
Volume
56
Number
7
Pages
1397-1411
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.
Keywords
Humans, Female, Menarche/genetics, Puberty/genetics, Gene Frequency, Animals, Multifactorial Inheritance/genetics, Mice, Genome-Wide Association Study, Adolescent, Puberty, Precocious/genetics, Polymorphism, Single Nucleotide, Receptors, G-Protein-Coupled/genetics, Puberty, Delayed/genetics, Child
Pubmed
Open Access
Yes
Create date
11/07/2024 15:50
Last modification date
20/07/2024 7:06
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