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 MR, 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 CL, Beckmann M, 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 P, 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 JJ, Hu FB, Hübner H, Hunter DJ, Jernström H, John EM, Karasik D, Khusnutdinova EK, Kristensen VN, Lacey JV, Lambrechts D, Launer LJ, Lind PA, Lindblom A, Magnusson PK, 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 SF, 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, Pharoah PD, 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 JR, Ong KK (2024)
Publication Language: English
Publication Type: Journal article
Publication year: 2024
Book Volume: 56
Pages Range: 1397-1411
Journal Issue: 7
DOI: 10.1038/s41588-024-01798-4
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.
APA:
Kentistou, K.A., Kaisinger, L.R., Stankovic, S., Vaudel, M., Mendes de Oliveira, E., Messina, A.,... Ong, K.K. (2024). Understanding the genetic complexity of puberty timing across the allele frequency spectrum. Nature Genetics, 56(7), 1397-1411. https://doi.org/10.1038/s41588-024-01798-4
MLA:
Kentistou, Katherine A., et al. "Understanding the genetic complexity of puberty timing across the allele frequency spectrum." Nature Genetics 56.7 (2024): 1397-1411.
BibTeX: Download