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Differential Impact of Genetic Loci on Age at Thelarche and Menarche in Healthy Girls

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@article{57ff073ead5248cba6a33470578a50e0,
title = "Differential Impact of Genetic Loci on Age at Thelarche and Menarche in Healthy Girls",
abstract = "Context: Recent genetic studies have identified genetic variants associated with age at pubertal onset. Whereas genome-wide association studies reported associations of several hundred genetic variants with timing of self-reported age at menarche, a recent clinical study focused on genetic variation affecting follicle-stimulating hormone action and clinically determined age at thelarche. The observations appear to be incongruent, as effect sizes varied substantially among the studies. Alternatively, this may point to a differential impact of specific genetic loci on distinct pubertal events.Objective: To investigate whether top-candidate genetic variants exhibit a different impact on timing of thelarche vs menarche, respectively.Design: Cross-sectional and longitudinal study of healthy girls.Setting: Population-based study in the Copenhagen area.Patients or Other Participants: Girls (1478) were followed through puberty and genotyped for FSHB c.-211G>T (rs10835638), FSHR c.-29G>A (rs1394205), FSHR c.2039A>G (rs6116), LIN28B (rs7759938), INHA (rs4141153), MKRN3 (rs12148769), TMEM38B (rs10453225), and ZNF483 (rs10980921).Main Outcome Measures: Clinical pubertal staging and anthropometric data.Results: We observed an association of LIN28B (rs7759938) with age at thelarche (P < 0.001, effect size: 0.27 year, 95{\%} confidence interval: 0.12 to 0.42) and age at menarche (P = 0.005, 0.17 year, 0.05 to 0.29). FSHB c.-211G>T (rs10835638) and FSHR c.-29G>A (rs1394205) minor allele count was associated with age at thelarche (P = 0.004, 0.19 year, 0.06 to 0.31) but not with age at menarche (P = 0.97; all adjusted for body mass index z scores).Conclusion: Our results indicate a differential impact of specific genetic loci on age at thelarche and menarche in healthy girls.",
keywords = "Journal Article",
author = "Busch, {Alexander S} and Hagen, {Casper P} and Maria Assens and Main, {Katharina M} and Kristian Almstrup and Anders Juul",
year = "2018",
month = "1",
day = "1",
doi = "10.1210/jc.2017-01860",
language = "English",
volume = "103",
pages = "228--234",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The/Endocrine Society",
number = "1",

}

RIS

TY - JOUR

T1 - Differential Impact of Genetic Loci on Age at Thelarche and Menarche in Healthy Girls

AU - Busch, Alexander S

AU - Hagen, Casper P

AU - Assens, Maria

AU - Main, Katharina M

AU - Almstrup, Kristian

AU - Juul, Anders

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Context: Recent genetic studies have identified genetic variants associated with age at pubertal onset. Whereas genome-wide association studies reported associations of several hundred genetic variants with timing of self-reported age at menarche, a recent clinical study focused on genetic variation affecting follicle-stimulating hormone action and clinically determined age at thelarche. The observations appear to be incongruent, as effect sizes varied substantially among the studies. Alternatively, this may point to a differential impact of specific genetic loci on distinct pubertal events.Objective: To investigate whether top-candidate genetic variants exhibit a different impact on timing of thelarche vs menarche, respectively.Design: Cross-sectional and longitudinal study of healthy girls.Setting: Population-based study in the Copenhagen area.Patients or Other Participants: Girls (1478) were followed through puberty and genotyped for FSHB c.-211G>T (rs10835638), FSHR c.-29G>A (rs1394205), FSHR c.2039A>G (rs6116), LIN28B (rs7759938), INHA (rs4141153), MKRN3 (rs12148769), TMEM38B (rs10453225), and ZNF483 (rs10980921).Main Outcome Measures: Clinical pubertal staging and anthropometric data.Results: We observed an association of LIN28B (rs7759938) with age at thelarche (P < 0.001, effect size: 0.27 year, 95% confidence interval: 0.12 to 0.42) and age at menarche (P = 0.005, 0.17 year, 0.05 to 0.29). FSHB c.-211G>T (rs10835638) and FSHR c.-29G>A (rs1394205) minor allele count was associated with age at thelarche (P = 0.004, 0.19 year, 0.06 to 0.31) but not with age at menarche (P = 0.97; all adjusted for body mass index z scores).Conclusion: Our results indicate a differential impact of specific genetic loci on age at thelarche and menarche in healthy girls.

AB - Context: Recent genetic studies have identified genetic variants associated with age at pubertal onset. Whereas genome-wide association studies reported associations of several hundred genetic variants with timing of self-reported age at menarche, a recent clinical study focused on genetic variation affecting follicle-stimulating hormone action and clinically determined age at thelarche. The observations appear to be incongruent, as effect sizes varied substantially among the studies. Alternatively, this may point to a differential impact of specific genetic loci on distinct pubertal events.Objective: To investigate whether top-candidate genetic variants exhibit a different impact on timing of thelarche vs menarche, respectively.Design: Cross-sectional and longitudinal study of healthy girls.Setting: Population-based study in the Copenhagen area.Patients or Other Participants: Girls (1478) were followed through puberty and genotyped for FSHB c.-211G>T (rs10835638), FSHR c.-29G>A (rs1394205), FSHR c.2039A>G (rs6116), LIN28B (rs7759938), INHA (rs4141153), MKRN3 (rs12148769), TMEM38B (rs10453225), and ZNF483 (rs10980921).Main Outcome Measures: Clinical pubertal staging and anthropometric data.Results: We observed an association of LIN28B (rs7759938) with age at thelarche (P < 0.001, effect size: 0.27 year, 95% confidence interval: 0.12 to 0.42) and age at menarche (P = 0.005, 0.17 year, 0.05 to 0.29). FSHB c.-211G>T (rs10835638) and FSHR c.-29G>A (rs1394205) minor allele count was associated with age at thelarche (P = 0.004, 0.19 year, 0.06 to 0.31) but not with age at menarche (P = 0.97; all adjusted for body mass index z scores).Conclusion: Our results indicate a differential impact of specific genetic loci on age at thelarche and menarche in healthy girls.

KW - Journal Article

U2 - 10.1210/jc.2017-01860

DO - 10.1210/jc.2017-01860

M3 - Journal article

VL - 103

SP - 228

EP - 234

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -

ID: 52695244