Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty

Cousminer, Diana L., Stergiakouli, Evangelia, Berry, Diane J., Ang, Wei, Groen-Blokhuis, Maria M., Koerner, Antje, Siitonen, Niina, Ntalla, Ioanna, Marinelli, Marcella, Perry, John R. B., Kettunen, Johannes, Jansen, Rick, Surakka, Ida, Timpson, Nicholas J., Ring, Susan, Mcmahon, George, Power, Chris, Wang, Carol, Kahonen, Mika, Viikari, Jorma, Lehtimaki, Terho, Middeldorp, Christel M., Pol, Hilleke E. Hulshoff, Neef, Madlen, Weise, Sebastian, Pahkala, Katja, Niinikoski, Harri, Zeggini, Eleftheria, Panoutsopoulou, Kalliope, Bustamante, Mariona, Penninx, Brenda W. J. H., Murabito, Joanne, Torrent, Maties, Dedoussis, George V., Kiess, Wieland, Boomsma, Dorret I., Pennell, Craig E., Raitakari, Olli T., Hyppoenen, Elina, Smith, George Davey, Ripatti, Samuli, McCarthy, Mark I., Widen, Elisabeth, Early Growth Genetics (EGG) Consortium and Warrington, Nicole M. (2014) Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty. Human Molecular Genetics, 23 16: 4452-4464. doi:10.1093/hmg/ddu150

Author Cousminer, Diana L.
Stergiakouli, Evangelia
Berry, Diane J.
Ang, Wei
Groen-Blokhuis, Maria M.
Koerner, Antje
Siitonen, Niina
Ntalla, Ioanna
Marinelli, Marcella
Perry, John R. B.
Kettunen, Johannes
Jansen, Rick
Surakka, Ida
Timpson, Nicholas J.
Ring, Susan
Mcmahon, George
Power, Chris
Wang, Carol
Kahonen, Mika
Viikari, Jorma
Lehtimaki, Terho
Middeldorp, Christel M.
Pol, Hilleke E. Hulshoff
Neef, Madlen
Weise, Sebastian
Pahkala, Katja
Niinikoski, Harri
Zeggini, Eleftheria
Panoutsopoulou, Kalliope
Bustamante, Mariona
Penninx, Brenda W. J. H.
Murabito, Joanne
Torrent, Maties
Dedoussis, George V.
Kiess, Wieland
Boomsma, Dorret I.
Pennell, Craig E.
Raitakari, Olli T.
Hyppoenen, Elina
Smith, George Davey
Ripatti, Samuli
McCarthy, Mark I.
Widen, Elisabeth
Early Growth Genetics (EGG) Consortium
Warrington, Nicole M.
Title Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 1460-2083
Publication date 2014-08-15
Year available 2014
Sub-type Article (original research)
DOI 10.1093/hmg/ddu150
Open Access Status Not Open Access
Volume 23
Issue 16
Start page 4452
End page 4464
Total pages 13
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Little is known about genes regulating male puberty. Further, while many identified pubertal timing 1variants associate with age at menarche, a late manifestation of puberty, and body mass, little is known about these variants' relationship to pubertal initiation or tempo. To address these questions, we performed genome-wide association meta-analysis in over 11 000 European samples with data on early pubertal traits, male genital and female breast development, measured by the Tanner scale. We report the first genome-wide significant locus for male sexual development upstream of myocardin-like 2 (MKL2) (P = 8.9×10-9), amenarche locus tagging a developmental pathway linking earlier puberty with reduced pubertal growth (P = 4.6×10-5) and short adult stature (p = 7.5×10-6) in both males and females. Furthermore, our results indicate that a proportion of menarche loci are important for pubertal initiation in both sexes. Consistent with epidemiological correlations between increased prepubertal body mass and earlier pubertal timing in girls, body mass index (BMI)-increasing alleles correlated with earlier breast development. In boys, some BMI-increasing alleles associated with earlier, and others with delayed, sexual development; these genetic results mimic the controversy in epidemiological studies, some of which show opposing correlations between prepubertal BMI and male puberty. Our results contribute to our understanding of the pubertal initiation program in both sexes and indicate that although mechanisms regulating pubertal onset in males and females may largely be shared, the relationship between body mass and pubertal timing in boys may be complex and requires further genetic studies.
Keyword Biochemistry & Molecular Biology
Genetics & Heredity
Biochemistry & Molecular Biology
Genetics & Heredity
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 120315
U01 DK062418
NIMH 1RC2MH089995-01
RC2 MH089951
NWO/SPI 56-464-14192
NWO 480-04-004
ZonMW 912-10-020
CRC1052/1 C05
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 31 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 11 Feb 2016, 22:39:56 EST by Nicole Warrington on behalf of Learning and Research Services (UQ Library)