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

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)451-460
Number of pages10
JournalAmerican Journal of Epidemiology
Volume178
Issue number3
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

Fingerprint

Menarche
Adiposity
Obesity
Single Nucleotide Polymorphism
Linear Models
Body Mass Index
Waist-Hip Ratio
Abdominal Obesity
Genome-Wide Association Study
Waist Circumference
Growth and Development
Research Personnel
Parturition
Weights and Measures
Population

Keywords

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

ASJC Scopus subject areas

  • Epidemiology

Cite this

Fernández-Rhodes, L., Demerath, E. W., Cousminer, D. L., Tao, R., Dreyfus, J. G., Esko, T., ... 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

Association of adiposity genetic variants with menarche timing in 92,105 women of European descent. / Fernández-Rhodes, Lindsay; Demerath, Ellen W.; Cousminer, Diana L.; Tao, Ran; Dreyfus, Jill G.; Esko, Tõnu; Smith, Albert V.; Gudnason, Vilmundur; Harris, Tamara B.; Launer, Lenore; McArdle, Patrick F.; Yerges-Armstrong, Laura M.; Elks, Cathy E.; Strachan, David P.; Kutalik, Zoltán; Vollenweider, Peter; Feenstra, Bjarke; Boyd, Heather A.; Metspalu, Andres; Mihailov, Evelin; Broer, Linda; Carola Zillikens, M.; Oostra, Ben; Van Duijn, Cornelia M.; Lunetta, Kathryn L.; Perry, John R B; Murray, Anna; Koller, Daniel L.; Lai, Dongbing; Corre, Tanguy; Toniolo, Daniela; Albrecht, Eva; Stöckl, Doris; Grallert, Harald; Gieger, Christian; Hayward, Caroline; Polasek, Ozren; Rudan, Igor; Wilson, James F.; He, Chunyan; Kraft, Peter; Hu, Frank B.; Hunter, David J.; Hottenga, Jouke Jan; Willemsen, Gonneke; Boomsma, Dorret I.; Byrne, Enda M.; Martin, Nicholas G.; Montgomery, Grant W.; Warrington, Nicole M.; Pennell, Craig E.; Stolk, Lisette; Visser, Jenny A.; Hofman, Albert; Uitterlinden, André G.; Rivadeneira, Fernando; Lin, Peng; Fisher, Sherri L.; Bierut, Laura J.; Crisponi, Laura; Porcu, Eleonora; Mangino, Massimo; Zhai, Guangju; Spector, Tim D.; Buring, Julie E.; Rose, Lynda M.; Ridker, Paul M.; Poole, Charles; Hirschhorn, Joel N.; Murabito, Joanne M.; Chasman, Daniel I.; Widen, Elisabeth; North, Kari E.; Ong, Ken K.; Franceschini, Nora.

In: American Journal of Epidemiology, Vol. 178, No. 3, 01.08.2013, p. 451-460.

Research output: Contribution to journalArticle

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
Fernández-Rhodes L, Demerath EW, Cousminer DL, Tao R, Dreyfus JG, Esko T et al. Association of adiposity genetic variants with menarche timing in 92,105 women of European descent. American Journal of Epidemiology. 2013 Aug 1;178(3):451-460. https://doi.org/10.1093/aje/kws473
Fernández-Rhodes, Lindsay ; Demerath, Ellen W. ; Cousminer, Diana L. ; Tao, Ran ; Dreyfus, Jill G. ; Esko, Tõnu ; Smith, Albert V. ; Gudnason, Vilmundur ; Harris, Tamara B. ; Launer, Lenore ; McArdle, Patrick F. ; Yerges-Armstrong, Laura M. ; Elks, Cathy E. ; Strachan, David P. ; Kutalik, Zoltán ; Vollenweider, Peter ; Feenstra, Bjarke ; Boyd, Heather A. ; Metspalu, Andres ; Mihailov, Evelin ; Broer, Linda ; Carola Zillikens, M. ; Oostra, Ben ; Van Duijn, Cornelia M. ; Lunetta, Kathryn L. ; Perry, John R B ; Murray, Anna ; Koller, Daniel L. ; Lai, Dongbing ; Corre, Tanguy ; Toniolo, Daniela ; Albrecht, Eva ; Stöckl, Doris ; Grallert, Harald ; Gieger, Christian ; Hayward, Caroline ; Polasek, Ozren ; Rudan, Igor ; Wilson, James F. ; He, Chunyan ; Kraft, Peter ; Hu, Frank B. ; Hunter, David J. ; Hottenga, Jouke Jan ; Willemsen, Gonneke ; Boomsma, Dorret I. ; Byrne, Enda M. ; Martin, Nicholas G. ; Montgomery, Grant W. ; Warrington, Nicole M. ; Pennell, Craig E. ; Stolk, Lisette ; Visser, Jenny A. ; Hofman, Albert ; Uitterlinden, André G. ; Rivadeneira, Fernando ; Lin, Peng ; Fisher, Sherri L. ; Bierut, Laura J. ; Crisponi, Laura ; Porcu, Eleonora ; Mangino, Massimo ; Zhai, Guangju ; Spector, Tim D. ; Buring, Julie E. ; Rose, Lynda M. ; Ridker, Paul M. ; Poole, Charles ; Hirschhorn, Joel N. ; Murabito, Joanne M. ; Chasman, Daniel I. ; Widen, Elisabeth ; North, Kari E. ; Ong, Ken K. ; Franceschini, Nora. / Association of adiposity genetic variants with menarche timing in 92,105 women of European descent. In: American Journal of Epidemiology. 2013 ; Vol. 178, No. 3. pp. 451-460.
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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

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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.

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KW - body mass index

KW - genetic association studies

KW - menarche

KW - obesity

KW - waist circumference

KW - waist:hip ratio

KW - women's health

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