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

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Title: Understanding the genetic complexity of puberty timing across the allele frequency spectrum
Authors: Kentistou, KA, Kaisinger, LR, Stankovic, S, Vaudel, M, Mendes de Oliveira, E, Messina, A, Walters, RG, Liu, X, Busch, AS, Helgason, H, Thompson, DJ, Santoni, F, Petricek, KM, Zouaghi, Y, Huang-Doran, I, Gudbjartsson, DF, Bratland, E, Lin, K, Gardner, EJ, Zhao, Y, Jia, RY, Terao, C, Riggan, MJ, Bolla, MK, Yazdanpanah, M, Yazdanpanah, N, Bradfield, JP, Broer, L, Campbell, A, Chasman, DI, Cousminer, DL, Franceschini, N, Franke, LH, Girotto, G, He, C, Järvelin, M-R, Joshi, PK, Kamatani, Y, Karlsson, R, Luan, J, Lunetta, KL, Mägi, R, Mangino, M, Medland, SE, Meisinger, C, Noordam, R, Nutile, T, Concas, MP, Polašek, O, Porcu, E, Ring, SM, Sala, C, Smith, AV, Tanaka, T, van der Most, PJ, Vitart, V, Wang, CA, Willemsen, G, Zygmunt, M, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Auer, PL, Barnes, CLK, Beckmann, MW, Berrington de Gonzalez, A, Bogdanova, NV, Bojesen, SE, Brenner, H, Buring, JE, Canzian, F, Chang-Claude, J, Couch, FJ, Cox, A, Crisponi, L, Czene, K, Daly, MB, Demerath, EW, Dennis, J, Devilee, P, De Vivo, I, Dörk, T, Dunning, AM, Dwek, M, Eriksson, JG, Fasching, PA, Fernandez-Rhodes, L, Ferreli, L, Fletcher, O, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, González-Neira, A, Grallert, H, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Hakonarson, H, Hart, RJ, Hickey, M, Hooning, MJ, Hoppe, R, Hopper, JL, Hottenga, J-J, Hu, FB, Huebner, H, Hunter, DJ, ABCTB Investigators, Jernström, H, John, EM, Karasik, D, Khusnutdinova, EK, Kristensen, VN, Lacey, JV, Lambrechts, D, Launer, LJ, Lind, PA, Lindblom, A, Magnusson, PKE, Mannermaa, A, McCarthy, MI, Meitinger, T, Menni, C, Michailidou, K, Millwood, IY, Milne, RL, Montgomery, GW, Nevanlinna, H, Nolte, IM, Nyholt, DR, Obi, N, O'Brien, KM, Offit, K, Oldehinkel, AJ, Ostrowski, SR, Palotie, A, Pedersen, OB, Peters, A, Pianigiani, G, Plaseska-Karanfilska, D, Pouta, A, Pozarickij, A, Radice, P, Rennert, G, Rosendaal, FR, Ruggiero, D, Saloustros, E, Sandler, DP, Schipf, S, Schmidt, CO, Schmidt, MK, Small, K, Spedicati, B, Stampfer, M, Stone, J, Tamimi, RM, Teras, LR, Tikkanen, E, Turman, C, Vachon, CM, Wang, Q, Winqvist, R, Wolk, A, Zemel, BS, Zheng, W, van Dijk, KW, Alizadeh, BZ, Bandinelli, S, Boerwinkle, E, Boomsma, DI, Ciullo, M, Chenevix-Trench, G, Cucca, F, Esko, T, Gieger, C, Grant, SFA, Gudnason, V, Hayward, C, Kolčić, I, Kraft, P, Lawlor, DA, Martin, NG, Nøhr, EA, Pedersen, NL, Pennell, CE, Ridker, PM, Robino, A, Snieder, H, Sovio, U, Spector, TD, Stöckl, D, Sudlow, C, Timpson, NJ, Toniolo, D, Uitterlinden, A, Ulivi, S, Völzke, H, Wareham, NJ, Widen, E, Wilson, JF, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group, Pharoah, PDP, Li, L, Easton, DF, Njølstad, PR, Sulem, P, Murabito, JM, Murray, A, Manousaki, D, Juul, A, Erikstrup, C, Stefansson, K, Horikoshi, M, Chen, Z, Farooqi, IS, Pitteloud, N, Johansson, S, Day, FR, Perry, JRB, Ong, KK
Publisher Information: Nature Research
Publication Year: 2024
Collection: The University of Melbourne: Digital Repository
Description: 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.
Document Type: article in journal/newspaper
Language: English
ISSN: 1061-4036
Relation: https://hdl.handle.net/11343/349381
Availability: https://hdl.handle.net/11343/349381
Rights: https://creativecommons.org/licenses/by/4.0 ; CC BY
Accession Number: edsbas.902C3961
Database: BASE
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  Data: Understanding the genetic complexity of puberty timing across the allele frequency spectrum
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– Name: Publisher
  Label: Publisher Information
  Group: PubInfo
  Data: Nature Research
– Name: DatePubCY
  Label: Publication Year
  Group: Date
  Data: 2024
– Name: Subset
  Label: Collection
  Group: HoldingsInfo
  Data: The University of Melbourne: Digital Repository
– Name: Abstract
  Label: Description
  Group: Ab
  Data: 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.
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: article in journal/newspaper
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 1061-4036
– Name: NoteTitleSource
  Label: Relation
  Group: SrcInfo
  Data: https://hdl.handle.net/11343/349381
– Name: URL
  Label: Availability
  Group: URL
  Data: https://hdl.handle.net/11343/349381
– Name: Copyright
  Label: Rights
  Group: Cpyrght
  Data: https://creativecommons.org/licenses/by/4.0 ; CC BY
– Name: AN
  Label: Accession Number
  Group: ID
  Data: edsbas.902C3961
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsbas&AN=edsbas.902C3961
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      – TitleFull: Understanding the genetic complexity of puberty timing across the allele frequency spectrum
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