Association of adiposity genetic variants with menarche timing in 92,105 women of European descent

Lindsay Fernández-Rhodes; Ellen W. Demerath; Diana L. Cousminer; Ran Tao; Jill G. Dreyfus; Tõnu Esko; Albert V. Smith; Vilmundur Gudnason; Tamara B. Harris; Lenore Launer; Patrick F. McArdle; Laura M. Yerges-Armstrong; Cathy E. Elks; David P. Strachan; Zoltán Kutalik; Peter Vollenweider; Bjarke Feenstra; Heather A. Boyd; Andres Metspalu; Evelin Mihailov; Linda Broer; M. Carola Zillikens; Ben Oostra; Cornelia M. Van Duijn; Kathryn L. Lunetta; John R.B. Perry; Anna Murray; Daniel L. Koller; Dongbing Lai; Tanguy Corre; Daniela Toniolo; Eva Albrecht; Doris Stöckl; Harald Grallert; Christian Gieger; Caroline Hayward; Ozren Polasek; Igor Rudan; James F. Wilson; Chunyan He; Peter Kraft; Frank B. Hu; David J. Hunter; Jouke Jan Hottenga; Gonneke Willemsen; Dorret I. Boomsma; Enda M. Byrne; Nicholas G. Martin; Grant W. Montgomery; Nicole M. Warrington; Craig E. Pennell; Lisette Stolk; Jenny A. Visser; Albert Hofman; André G. Uitterlinden; Fernando Rivadeneira; Peng Lin; Sherri L. Fisher; Laura J. Bierut; Laura Crisponi; Eleonora Porcu; Massimo Mangino; Guangju Zhai; Tim D. Spector; Julie E. Buring; Lynda M. Rose; Paul M. Ridker; Charles Poole; Joel N. Hirschhorn; Joanne M. Murabito; Daniel I. Chasman; Elisabeth Widen; Kari E. North; Ken K. Ong; Nora Franceschini

doi:10.1093/aje/kws473

Association of adiposity genetic variants with menarche timing in 92,105 women of European descent

Lindsay Fernández-Rhodes, Ellen W. Demerath, Diana L. Cousminer, Ran Tao, Jill G. Dreyfus, Tõnu Esko, Albert V. Smith, Vilmundur Gudnason, Tamara B. Harris, Lenore Launer, Patrick F. McArdle, Laura M. Yerges-Armstrong, Cathy E. Elks, David P. Strachan, Zoltán Kutalik, Peter Vollenweider, Bjarke Feenstra, Heather A. Boyd, Andres Metspalu, Evelin MihailovLinda Broer, M. Carola Zillikens, Ben Oostra, Cornelia M. Van Duijn, Kathryn L. Lunetta, John R.B. Perry, Anna Murray, Daniel L. Koller, Dongbing Lai, Tanguy Corre, Daniela Toniolo, Eva Albrecht, Doris Stöckl, Harald Grallert, Christian Gieger, Caroline Hayward, Ozren Polasek, Igor Rudan, James F. Wilson, Chunyan He, Peter Kraft, Frank B. Hu, David J. Hunter, Jouke Jan Hottenga, Gonneke Willemsen, Dorret I. Boomsma, Enda M. Byrne, Nicholas G. Martin, Grant W. Montgomery, Nicole M. Warrington, Craig E. Pennell, Lisette Stolk, Jenny A. Visser, Albert Hofman, André G. Uitterlinden, Fernando Rivadeneira, Peng Lin, Sherri L. Fisher, Laura J. Bierut, Laura Crisponi, Eleonora Porcu, Massimo Mangino, Guangju Zhai, Tim D. Spector, Julie E. Buring, Lynda M. Rose, Paul M. Ridker, Charles Poole, Joel N. Hirschhorn, Joanne M. Murabito, Daniel I. Chasman, Elisabeth Widen, Kari E. North, Ken K. Ong, Nora Franceschini

Markey Cancer Center / Cancer Research Priority Initiative

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

Abstract

Obesity is of global health concern. There are well-described inverse relationships between female pubertal timing and obesity. Recent genome-wide association studies of age at menarche identified several obesity-related variants. Using data from the ReproGen Consortium, we employed meta-analytical techniques to estimate the associations of 95 a priori and recently identified obesity-related (body mass index (weight (kg)/height (m)²), waist circumference, and waist:hip ratio) single-nucleotide polymorphisms (SNPs) with age at menarche in 92,116 women of European descent from 38 studies (1970-2010), in order to estimate associations between genetic variants associated with central or overall adiposity and pubertal timing in girls. Investigators in each study performed a separate analysis of associations between the selected SNPs and age at menarche (ages 9-17 years) using linear regression models and adjusting for birth year, site (as appropriate), and population stratification. Heterogeneity of effect-measure estimates was investigated using meta-regression. Six novel associations of body mass index loci with age at menarche were identified, and 11 adiposity loci previously reported to be associated with age at menarche were confirmed, but none of the central adiposity variants individually showed significant associations. These findings suggest complex genetic relationships between menarche and overall obesity, and to a lesser extent central obesity, in normal processes of growth and development.

Original language	English
Pages (from-to)	451-460
Number of pages	10
Journal	American Journal of Epidemiology
Volume	178
Issue number	3
DOIs	https://doi.org/10.1093/aje/kws473
State	Published - Aug 1 2013

Funding

Funders	Funder number
National Institute on Drug Abuse	R01DA013423

Keywords

adiposity
body mass index
genetic association studies
menarche
obesity
waist circumference
waist:hip ratio
women's health

ASJC Scopus subject areas

Epidemiology

UN SDGs

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

Access to Document

10.1093/aje/kws473

Cite this

Fernández-Rhodes, L., Demerath, E. W., Cousminer, D. L., Tao, R., Dreyfus, J. G., Esko, T., Smith, A. V., Gudnason, V., Harris, T. B., Launer, L., McArdle, P. F., Yerges-Armstrong, L. M., Elks, C. E., Strachan, D. P., Kutalik, Z., Vollenweider, P., Feenstra, B., Boyd, H. A., Metspalu, A., ... Franceschini, N. (2013). Association of adiposity genetic variants with menarche timing in 92,105 women of European descent. American Journal of Epidemiology, 178(3), 451-460. https://doi.org/10.1093/aje/kws473

@article{bfca959455a34acd8adf38912d22de55,

title = "Association of adiposity genetic variants with menarche timing in 92,105 women of European descent",

abstract = "Obesity is of global health concern. There are well-described inverse relationships between female pubertal timing and obesity. Recent genome-wide association studies of age at menarche identified several obesity-related variants. Using data from the ReproGen Consortium, we employed meta-analytical techniques to estimate the associations of 95 a priori and recently identified obesity-related (body mass index (weight (kg)/height (m)2), waist circumference, and waist:hip ratio) single-nucleotide polymorphisms (SNPs) with age at menarche in 92,116 women of European descent from 38 studies (1970-2010), in order to estimate associations between genetic variants associated with central or overall adiposity and pubertal timing in girls. Investigators in each study performed a separate analysis of associations between the selected SNPs and age at menarche (ages 9-17 years) using linear regression models and adjusting for birth year, site (as appropriate), and population stratification. Heterogeneity of effect-measure estimates was investigated using meta-regression. Six novel associations of body mass index loci with age at menarche were identified, and 11 adiposity loci previously reported to be associated with age at menarche were confirmed, but none of the central adiposity variants individually showed significant associations. These findings suggest complex genetic relationships between menarche and overall obesity, and to a lesser extent central obesity, in normal processes of growth and development.",

keywords = "adiposity, body mass index, genetic association studies, menarche, obesity, waist circumference, waist:hip ratio, women's health",

author = "Lindsay Fern{\'a}ndez-Rhodes and Demerath, \{Ellen W.\} and Cousminer, \{Diana L.\} and Ran Tao and Dreyfus, \{Jill G.\} and T{\~o}nu Esko and Smith, \{Albert V.\} and Vilmundur Gudnason and Harris, \{Tamara B.\} and Lenore Launer and McArdle, \{Patrick F.\} and Yerges-Armstrong, \{Laura M.\} and Elks, \{Cathy E.\} and Strachan, \{David P.\} and Zolt{\'a}n Kutalik and Peter Vollenweider and Bjarke Feenstra and Boyd, \{Heather A.\} and Andres Metspalu and Evelin Mihailov and Linda Broer and \{Carola Zillikens\}, M. and Ben Oostra and \{Van Duijn\}, \{Cornelia M.\} and Lunetta, \{Kathryn L.\} and Perry, \{John R.B.\} and Anna Murray and Koller, \{Daniel L.\} and Dongbing Lai and Tanguy Corre and Daniela Toniolo and Eva Albrecht and Doris St{\"o}ckl and Harald Grallert and Christian Gieger and Caroline Hayward and Ozren Polasek and Igor Rudan and Wilson, \{James F.\} and Chunyan He and Peter Kraft and Hu, \{Frank B.\} and Hunter, \{David J.\} and Hottenga, \{Jouke Jan\} and Gonneke Willemsen and Boomsma, \{Dorret I.\} and Byrne, \{Enda M.\} and Martin, \{Nicholas G.\} and Montgomery, \{Grant W.\} and Warrington, \{Nicole M.\} and Pennell, \{Craig E.\} and Lisette Stolk and Visser, \{Jenny A.\} and Albert Hofman and Uitterlinden, \{Andr{\'e} G.\} and Fernando Rivadeneira and Peng Lin and Fisher, \{Sherri L.\} and Bierut, \{Laura J.\} and Laura Crisponi and Eleonora Porcu and Massimo Mangino and Guangju Zhai and Spector, \{Tim D.\} and Buring, \{Julie E.\} and Rose, \{Lynda M.\} and Ridker, \{Paul M.\} and Charles Poole and Hirschhorn, \{Joel N.\} and Murabito, \{Joanne M.\} and Chasman, \{Daniel I.\} and Elisabeth Widen and North, \{Kari E.\} and Ong, \{Ken K.\} and Nora Franceschini",

year = "2013",

month = aug,

day = "1",

doi = "10.1093/aje/kws473",

language = "English",

volume = "178",

pages = "451--460",

number = "3",

}

Fernández-Rhodes, L, Demerath, EW, Cousminer, DL, Tao, R, Dreyfus, JG, Esko, T, Smith, AV, Gudnason, V, Harris, TB, Launer, L, McArdle, PF, Yerges-Armstrong, LM, Elks, CE, Strachan, DP, Kutalik, Z, Vollenweider, P, Feenstra, B, Boyd, HA, Metspalu, A, Mihailov, E, Broer, L, Carola Zillikens, M, Oostra, B, Van Duijn, CM, Lunetta, KL, Perry, JRB, Murray, A, Koller, DL, Lai, D, Corre, T, Toniolo, D, Albrecht, E, Stöckl, D, Grallert, H, Gieger, C, Hayward, C, Polasek, O, Rudan, I, Wilson, JF, He, C, Kraft, P, Hu, FB, Hunter, DJ, Hottenga, JJ, Willemsen, G, Boomsma, DI, Byrne, EM, Martin, NG, Montgomery, GW, Warrington, NM, Pennell, CE, Stolk, L, Visser, JA, Hofman, A, Uitterlinden, AG, Rivadeneira, F, Lin, P, Fisher, SL, Bierut, LJ, Crisponi, L, Porcu, E, Mangino, M, Zhai, G, Spector, TD, Buring, JE, Rose, LM, Ridker, PM, Poole, C, Hirschhorn, JN, Murabito, JM, Chasman, DI, Widen, E, North, KE, Ong, KK & Franceschini, N 2013, 'Association of adiposity genetic variants with menarche timing in 92,105 women of European descent', American Journal of Epidemiology, vol. 178, no. 3, pp. 451-460. https://doi.org/10.1093/aje/kws473

TY - JOUR

T1 - Association of adiposity genetic variants with menarche timing in 92,105 women of European descent

AU - Fernández-Rhodes, Lindsay

AU - Demerath, Ellen W.

AU - Cousminer, Diana L.

AU - Tao, Ran

AU - Dreyfus, Jill G.

AU - Esko, Tõnu

AU - Smith, Albert V.

AU - Gudnason, Vilmundur

AU - Harris, Tamara B.

AU - Launer, Lenore

AU - McArdle, Patrick F.

AU - Yerges-Armstrong, Laura M.

AU - Elks, Cathy E.

AU - Strachan, David P.

AU - Kutalik, Zoltán

AU - Vollenweider, Peter

AU - Feenstra, Bjarke

AU - Boyd, Heather A.

AU - Metspalu, Andres

AU - Mihailov, Evelin

AU - Broer, Linda

AU - Carola Zillikens, M.

AU - Oostra, Ben

AU - Van Duijn, Cornelia M.

AU - Lunetta, Kathryn L.

AU - Perry, John R.B.

AU - Murray, Anna

AU - Koller, Daniel L.

AU - Lai, Dongbing

AU - Corre, Tanguy

AU - Toniolo, Daniela

AU - Albrecht, Eva

AU - Stöckl, Doris

AU - Grallert, Harald

AU - Gieger, Christian

AU - Hayward, Caroline

AU - Polasek, Ozren

AU - Rudan, Igor

AU - Wilson, James F.

AU - He, Chunyan

AU - Kraft, Peter

AU - Hu, Frank B.

AU - Hunter, David J.

AU - Hottenga, Jouke Jan

AU - Willemsen, Gonneke

AU - Boomsma, Dorret I.

AU - Byrne, Enda M.

AU - Martin, Nicholas G.

AU - Montgomery, Grant W.

AU - Warrington, Nicole M.

AU - Pennell, Craig E.

AU - Stolk, Lisette

AU - Visser, Jenny A.

AU - Hofman, Albert

AU - Uitterlinden, André G.

AU - Rivadeneira, Fernando

AU - Lin, Peng

AU - Fisher, Sherri L.

AU - Bierut, Laura J.

AU - Crisponi, Laura

AU - Porcu, Eleonora

AU - Mangino, Massimo

AU - Zhai, Guangju

AU - Spector, Tim D.

AU - Buring, Julie E.

AU - Rose, Lynda M.

AU - Ridker, Paul M.

AU - Poole, Charles

AU - Hirschhorn, Joel N.

AU - Murabito, Joanne M.

AU - Chasman, Daniel I.

AU - Widen, Elisabeth

AU - North, Kari E.

AU - Ong, Ken K.

AU - Franceschini, Nora

PY - 2013/8/1

Y1 - 2013/8/1

N2 - Obesity is of global health concern. There are well-described inverse relationships between female pubertal timing and obesity. Recent genome-wide association studies of age at menarche identified several obesity-related variants. Using data from the ReproGen Consortium, we employed meta-analytical techniques to estimate the associations of 95 a priori and recently identified obesity-related (body mass index (weight (kg)/height (m)2), waist circumference, and waist:hip ratio) single-nucleotide polymorphisms (SNPs) with age at menarche in 92,116 women of European descent from 38 studies (1970-2010), in order to estimate associations between genetic variants associated with central or overall adiposity and pubertal timing in girls. Investigators in each study performed a separate analysis of associations between the selected SNPs and age at menarche (ages 9-17 years) using linear regression models and adjusting for birth year, site (as appropriate), and population stratification. Heterogeneity of effect-measure estimates was investigated using meta-regression. Six novel associations of body mass index loci with age at menarche were identified, and 11 adiposity loci previously reported to be associated with age at menarche were confirmed, but none of the central adiposity variants individually showed significant associations. These findings suggest complex genetic relationships between menarche and overall obesity, and to a lesser extent central obesity, in normal processes of growth and development.

AB - Obesity is of global health concern. There are well-described inverse relationships between female pubertal timing and obesity. Recent genome-wide association studies of age at menarche identified several obesity-related variants. Using data from the ReproGen Consortium, we employed meta-analytical techniques to estimate the associations of 95 a priori and recently identified obesity-related (body mass index (weight (kg)/height (m)2), waist circumference, and waist:hip ratio) single-nucleotide polymorphisms (SNPs) with age at menarche in 92,116 women of European descent from 38 studies (1970-2010), in order to estimate associations between genetic variants associated with central or overall adiposity and pubertal timing in girls. Investigators in each study performed a separate analysis of associations between the selected SNPs and age at menarche (ages 9-17 years) using linear regression models and adjusting for birth year, site (as appropriate), and population stratification. Heterogeneity of effect-measure estimates was investigated using meta-regression. Six novel associations of body mass index loci with age at menarche were identified, and 11 adiposity loci previously reported to be associated with age at menarche were confirmed, but none of the central adiposity variants individually showed significant associations. These findings suggest complex genetic relationships between menarche and overall obesity, and to a lesser extent central obesity, in normal processes of growth and development.

KW - adiposity

KW - body mass index

KW - genetic association studies

KW - menarche

KW - obesity

KW - waist circumference

KW - waist:hip ratio

KW - women's health

UR - https://www.scopus.com/pages/publications/84881168299

UR - https://www.scopus.com/inward/citedby.url?scp=84881168299&partnerID=8YFLogxK

U2 - 10.1093/aje/kws473

DO - 10.1093/aje/kws473

M3 - Article

C2 - 23558354

AN - SCOPUS:84881168299

SN - 0002-9262

VL - 178

SP - 451

EP - 460

JO - American Journal of Epidemiology

JF - American Journal of Epidemiology

IS - 3

ER -

Association of adiposity genetic variants with menarche timing in 92,105 women of European descent

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Keywords

ASJC Scopus subject areas

UN SDGs

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