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

Research output: Contribution to journal › Journal article › Research › peer-review

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Understanding the genetic complexity of puberty timing across the allele frequency spectrum. / Kentistou, Katherine A.; Kaisinger, Lena R.; Stankovic, Stasa; Vaudel, Marc; Mendes de Oliveira, Edson; Messina, Andrea; Walters, Robin G.; Liu, Xiaoxi; Busch, Alexander S.; Helgason, Hannes; Thompson, Deborah J.; Santoni, Federico; Petricek, Konstantin M.; Zouaghi, Yassine; Huang-Doran, Isabel; Gudbjartsson, Daniel F.; Bratland, Eirik; Lin, Kuang; Gardner, Eugene J.; Zhao, Yajie; Jia, Raina Y.; Terao, Chikashi; Riggan, Marjorie J.; Bolla, Manjeet K.; Yazdanpanah, Mojgan; Yazdanpanah, Nahid; Bradfield, Jonathan P.; Broer, Linda; Campbell, Archie; Chasman, Daniel I.; Cousminer, Diana L.; Franceschini, Nora; Franke, Lude H.; Girotto, Giorgia; He, Chunyan; Järvelin, Marjo Riitta; Joshi, Peter K.; Kamatani, Yoichiro; Karlsson, Robert; Luan, Jian’an; Lunetta, Kathryn L.; Mägi, Reedik; Mangino, Massimo; Medland, Sarah E.; Bojesen, Stig E.; Ostrowski, Sisse R.; Pedersen, Ole B.; Wang, Qin; Nøhr, Ellen A.; Juul, Anders.

In: Nature Genetics, Vol. 56, No. 7, 2024, p. 1397-1411.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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, Bojesen, SE, Ostrowski, SR, Pedersen, OB, Wang, Q, Nøhr, EA & Juul, A 2024, 'Understanding the genetic complexity of puberty timing across the allele frequency spectrum', Nature Genetics, vol. 56, no. 7, pp. 1397-1411. https://doi.org/10.1038/s41588-024-01798-4

APA

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., ... Juul, A. (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

Vancouver

Kentistou KA, Kaisinger LR, Stankovic S, Vaudel M, Mendes de Oliveira E, Messina A et al. Understanding the genetic complexity of puberty timing across the allele frequency spectrum. Nature Genetics. 2024;56(7):1397-1411. https://doi.org/10.1038/s41588-024-01798-4

Author

Kentistou, Katherine A. ; Kaisinger, Lena R. ; Stankovic, Stasa ; Vaudel, Marc ; Mendes de Oliveira, Edson ; Messina, Andrea ; Walters, Robin G. ; Liu, Xiaoxi ; Busch, Alexander S. ; Helgason, Hannes ; Thompson, Deborah J. ; Santoni, Federico ; Petricek, Konstantin M. ; Zouaghi, Yassine ; Huang-Doran, Isabel ; Gudbjartsson, Daniel F. ; Bratland, Eirik ; Lin, Kuang ; Gardner, Eugene J. ; Zhao, Yajie ; Jia, Raina Y. ; Terao, Chikashi ; Riggan, Marjorie J. ; Bolla, Manjeet K. ; Yazdanpanah, Mojgan ; Yazdanpanah, Nahid ; Bradfield, Jonathan P. ; Broer, Linda ; Campbell, Archie ; Chasman, Daniel I. ; Cousminer, Diana L. ; Franceschini, Nora ; Franke, Lude H. ; Girotto, Giorgia ; He, Chunyan ; Järvelin, Marjo Riitta ; Joshi, Peter K. ; Kamatani, Yoichiro ; Karlsson, Robert ; Luan, Jian’an ; Lunetta, Kathryn L. ; Mägi, Reedik ; Mangino, Massimo ; Medland, Sarah E. ; Bojesen, Stig E. ; Ostrowski, Sisse R. ; Pedersen, Ole B. ; Wang, Qin ; Nøhr, Ellen A. ; Juul, Anders. / Understanding the genetic complexity of puberty timing across the allele frequency spectrum. In: Nature Genetics. 2024 ; Vol. 56, No. 7. pp. 1397-1411.

Bibtex

@article{a6cc51d0ad744228b2a6700396086b09,
title = "Understanding the genetic complexity of puberty timing across the allele frequency spectrum",
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.",
author = "Kentistou, {Katherine A.} and Kaisinger, {Lena R.} and Stasa Stankovic and Marc Vaudel and {Mendes de Oliveira}, Edson and Andrea Messina and Walters, {Robin G.} and Xiaoxi Liu and Busch, {Alexander S.} and Hannes Helgason and Thompson, {Deborah J.} and Federico Santoni and Petricek, {Konstantin M.} and Yassine Zouaghi and Isabel Huang-Doran and Gudbjartsson, {Daniel F.} and Eirik Bratland and Kuang Lin and Gardner, {Eugene J.} and Yajie Zhao and Jia, {Raina Y.} and Chikashi Terao and Riggan, {Marjorie J.} and Bolla, {Manjeet K.} and Mojgan Yazdanpanah and Nahid Yazdanpanah and Bradfield, {Jonathan P.} and Linda Broer and Archie Campbell and Chasman, {Daniel I.} and Cousminer, {Diana L.} and Nora Franceschini and Franke, {Lude H.} and Giorgia Girotto and Chunyan He and J{\"a}rvelin, {Marjo Riitta} and Joshi, {Peter K.} and Yoichiro Kamatani and Robert Karlsson and Jian{\textquoteright}an Luan and Lunetta, {Kathryn L.} and Reedik M{\"a}gi and Massimo Mangino and Medland, {Sarah E.} and Bojesen, {Stig E.} and Ostrowski, {Sisse R.} and Pedersen, {Ole B.} and Qin Wang and N{\o}hr, {Ellen A.} and Anders Juul",
note = "Publisher Copyright: {\textcopyright} The Author(s) 2024. corrected publication 2024.",
year = "2024",
doi = "10.1038/s41588-024-01798-4",
language = "English",
volume = "56",
pages = "1397--1411",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "7",

}

RIS

TY - JOUR

T1 - Understanding the genetic complexity of puberty timing across the allele frequency spectrum

AU - Kentistou, Katherine A.

AU - Kaisinger, Lena R.

AU - Stankovic, Stasa

AU - Vaudel, Marc

AU - Mendes de Oliveira, Edson

AU - Messina, Andrea

AU - Walters, Robin G.

AU - Liu, Xiaoxi

AU - Busch, Alexander S.

AU - Helgason, Hannes

AU - Thompson, Deborah J.

AU - Santoni, Federico

AU - Petricek, Konstantin M.

AU - Zouaghi, Yassine

AU - Huang-Doran, Isabel

AU - Gudbjartsson, Daniel F.

AU - Bratland, Eirik

AU - Lin, Kuang

AU - Gardner, Eugene J.

AU - Zhao, Yajie

AU - Jia, Raina Y.

AU - Terao, Chikashi

AU - Riggan, Marjorie J.

AU - Bolla, Manjeet K.

AU - Yazdanpanah, Mojgan

AU - Yazdanpanah, Nahid

AU - Bradfield, Jonathan P.

AU - Broer, Linda

AU - Campbell, Archie

AU - Chasman, Daniel I.

AU - Cousminer, Diana L.

AU - Franceschini, Nora

AU - Franke, Lude H.

AU - Girotto, Giorgia

AU - He, Chunyan

AU - Järvelin, Marjo Riitta

AU - Joshi, Peter K.

AU - Kamatani, Yoichiro

AU - Karlsson, Robert

AU - Luan, Jian’an

AU - Lunetta, Kathryn L.

AU - Mägi, Reedik

AU - Mangino, Massimo

AU - Medland, Sarah E.

AU - Bojesen, Stig E.

AU - Ostrowski, Sisse R.

AU - Pedersen, Ole B.

AU - Wang, Qin

AU - Nøhr, Ellen A.

AU - Juul, Anders

N1 - Publisher Copyright: © The Author(s) 2024. corrected publication 2024.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

U2 - 10.1038/s41588-024-01798-4

DO - 10.1038/s41588-024-01798-4

M3 - Journal article

C2 - 38951643

AN - SCOPUS:85199125224

VL - 56

SP - 1397

EP - 1411

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7

ER -

ID: 399728112