Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

Cathy E Elks; John R B Perry; Patrick Sulem; Daniel I Chasman; Nora Franceschini; Chunyan He; Kathryn L Lunetta; Jenny A Visser; Enda M Byrne; Diana L Cousminer; Daniel F Gudbjartsson; Tõnu Esko; Bjarke Feenstra; Jouke-Jan Hottenga; Daniel L Koller; Zoltán Kutalik; Peng Lin; Massimo Mangino; Mara Marongiu; Patrick F McArdle; Albert V Smith; Lisette Stolk; Sophie H van Wingerden; Jing Hua Zhao; Eva Albrecht; Tanguy Corre; Erik Ingelsson; Caroline Hayward; Patrik K E Magnusson; Erin N Smith; Shelia Ulivi; Nicole M Warrington; Lina Zgaga; Helen Alavere; Najaf Amin; Thor Aspelund; Stefania Bandinelli; Inês Barroso; Gerald S Berenson; Sven Bergmann; Hannah Blackburn; Eric Boerwinkle; Julie E Buring; Fabio Busonero; Harry Campbell; Stephen J Chanock; Wei Chen; Marilyn C Cornelis; David Couper; Tuomas Oskari Kilpeläinen; GIANT Consortium

doi:10.1038/ng.714

Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

Cathy E Elks, John R B Perry, Patrick Sulem, Daniel I Chasman, Nora Franceschini, Chunyan He, Kathryn L Lunetta, Jenny A Visser, Enda M Byrne, Diana L Cousminer, Daniel F Gudbjartsson, Tõnu Esko, Bjarke Feenstra, Jouke-Jan Hottenga, Daniel L Koller, Zoltán Kutalik, Peng Lin, Massimo Mangino, Mara Marongiu, Patrick F McArdleAlbert V Smith, Lisette Stolk, Sophie H van Wingerden, Jing Hua Zhao, Eva Albrecht, Tanguy Corre, Erik Ingelsson, Caroline Hayward, Patrik K E Magnusson, Erin N Smith, Shelia Ulivi, Nicole M Warrington, Lina Zgaga, Helen Alavere, Najaf Amin, Thor Aspelund, Stefania Bandinelli, Inês Barroso, Gerald S Berenson, Sven Bergmann, Hannah Blackburn, Eric Boerwinkle, Julie E Buring, Fabio Busonero, Harry Campbell, Stephen J Chanock, Wei Chen, Marilyn C Cornelis, David Couper, Tuomas Oskari Kilpeläinen, GIANT Consortium

356 Citations (Scopus)

Abstract

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10 -60) and 9q31.2 (P = 2.2 × 10 -33), we identified 30 new menarche loci (all P < 5 × 10 -8) and found suggestive evidence for a further 10 loci (P < 1.9 × 10 -6). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

Original language	English
Journal	Nature Genetics
Volume	42
Issue number	12
Pages (from-to)	1077-85
Number of pages	9
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.714
Publication status	Published - 1 Dec 2010

Keywords

Adolescent
Aging
Body Height
Body Size
Child
DNA Copy Number Variations
Female
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Inheritance Patterns
Menarche
Obesity
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Reproducibility of Results
Time Factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.714

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Elks, C. E., Perry, J. R. B., Sulem, P., Chasman, D. I., Franceschini, N., He, C., Lunetta, K. L., Visser, J. A., Byrne, E. M., Cousminer, D. L., Gudbjartsson, D. F., Esko, T., Feenstra, B., Hottenga, J-J., Koller, D. L., Kutalik, Z., Lin, P., Mangino, M., Marongiu, M., ... GIANT Consortium (2010). Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nature Genetics, 42(12), 1077-85. https://doi.org/10.1038/ng.714

Elks, CE, Perry, JRB, Sulem, P, Chasman, DI, Franceschini, N, He, C, Lunetta, KL, Visser, JA, Byrne, EM, Cousminer, DL, Gudbjartsson, DF, Esko, T, Feenstra, B, Hottenga, J-J, Koller, DL, Kutalik, Z, Lin, P, Mangino, M, Marongiu, M, McArdle, PF, Smith, AV, Stolk, L, van Wingerden, SH, Zhao, JH, Albrecht, E, Corre, T, Ingelsson, E, Hayward, C, Magnusson, PKE, Smith, EN, Ulivi, S, Warrington, NM, Zgaga, L, Alavere, H, Amin, N, Aspelund, T, Bandinelli, S, Barroso, I, Berenson, GS, Bergmann, S, Blackburn, H, Boerwinkle, E, Buring, JE, Busonero, F, Campbell, H, Chanock, SJ, Chen, W, Cornelis, MC, Couper, D, Oskari Kilpeläinen, T & GIANT Consortium 2010, 'Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies', Nature Genetics, vol. 42, no. 12, pp. 1077-85. https://doi.org/10.1038/ng.714

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abstract = "To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10 -60) and 9q31.2 (P = 2.2 × 10 -33), we identified 30 new menarche loci (all P < 5 × 10 -8) and found suggestive evidence for a further 10 loci (P < 1.9 × 10 -6). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.",

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AU - Elks, Cathy E

AU - Perry, John R B

AU - Sulem, Patrick

AU - Chasman, Daniel I

AU - Franceschini, Nora

AU - He, Chunyan

AU - Lunetta, Kathryn L

AU - Visser, Jenny A

AU - Byrne, Enda M

AU - Cousminer, Diana L

AU - Gudbjartsson, Daniel F

AU - Esko, Tõnu

AU - Feenstra, Bjarke

AU - Hottenga, Jouke-Jan

AU - Koller, Daniel L

AU - Kutalik, Zoltán

AU - Lin, Peng

AU - Mangino, Massimo

AU - Marongiu, Mara

AU - McArdle, Patrick F

AU - Smith, Albert V

AU - Stolk, Lisette

AU - van Wingerden, Sophie H

AU - Zhao, Jing Hua

AU - Albrecht, Eva

AU - Corre, Tanguy

AU - Ingelsson, Erik

AU - Hayward, Caroline

AU - Magnusson, Patrik K E

AU - Smith, Erin N

AU - Ulivi, Shelia

AU - Warrington, Nicole M

AU - Zgaga, Lina

AU - Alavere, Helen

AU - Amin, Najaf

AU - Aspelund, Thor

AU - Bandinelli, Stefania

AU - Barroso, Inês

AU - Berenson, Gerald S

AU - Bergmann, Sven

AU - Blackburn, Hannah

AU - Boerwinkle, Eric

AU - Buring, Julie E

AU - Busonero, Fabio

AU - Campbell, Harry

AU - Chanock, Stephen J

AU - Chen, Wei

AU - Cornelis, Marilyn C

AU - Couper, David

AU - Oskari Kilpeläinen, Tuomas

AU - GIANT Consortium

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N2 - To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10 -60) and 9q31.2 (P = 2.2 × 10 -33), we identified 30 new menarche loci (all P < 5 × 10 -8) and found suggestive evidence for a further 10 loci (P < 1.9 × 10 -6). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

AB - To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10 -60) and 9q31.2 (P = 2.2 × 10 -33), we identified 30 new menarche loci (all P < 5 × 10 -8) and found suggestive evidence for a further 10 loci (P < 1.9 × 10 -6). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

KW - Adolescent

KW - Aging

KW - Body Height

KW - Body Size

KW - Child

KW - DNA Copy Number Variations

KW - Female

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Inheritance Patterns

KW - Menarche

KW - Obesity

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - Reproducibility of Results

KW - Time Factors

U2 - 10.1038/ng.714

DO - 10.1038/ng.714

M3 - Journal article

C2 - 21102462

SN - 1061-4036

VL - 42

SP - 1077

EP - 1085

JO - Nature: New biology

JF - Nature: New biology

IS - 12

ER -

Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

Abstract

Keywords

UN SDGs

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