Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

A Polygenic Risk Score Suggests Shared Genetic Architecture of Voice Break With Early Markers of Pubertal Onset in Boys

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{9f8546213e6f4da08f8227c935a52c79,
title = "A Polygenic Risk Score Suggests Shared Genetic Architecture of Voice Break With Early Markers of Pubertal Onset in Boys",
abstract = "CONTEXT: Voice break, as a landmark of advanced male puberty in genome-wide association studies (GWAS), has revealed that pubertal timing is a highly polygenic trait. Although voice break is easily recorded in large cohorts, it holds quite low precision as a marker of puberty. In contrast, gonadarche and pubarche are early and clinically well-defined measures of puberty onset.OBJECTIVE: To determine whether a polygenic risk score (PRS) of alleles that confer risk for voice break associates with age at gonadarche (AAG) and age at pubarche (AAP) in Chilean boys.EXPERIMENTAL DESIGN: Longitudinal study.SUBJECTS AND METHODS: 401 boys from the Growth and Obesity Chilean Cohort Study (n = 1194; 49.2{\%} boys).MAIN OUTCOME MEASURES: Biannual clinical pubertal staging including orchidometry. AAG and AAP were estimated by censoring methods. Genotyping was performed using the Multi-Ethnic Global Array (Illumina). Using GWAS summary statistics from the UK-Biobank, 29 significant and independent single nucleotide polymorphisms associated with age at voice break were extracted. Individual PRS were computed as the sum of risk alleles weighted by the effect size.RESULTS: The PRS was associated with AAG (β=0.01, P = 0.04) and AAP (β=0.185, P = 0.0004). In addition, boys within the 20{\%} highest PRS experienced gonadarche and pubarche 0.55 and 0.67 years later than those in the lowest 20{\%}, respectively (P = 0.013 and P = 0.007).CONCLUSIONS: Genetic variants identified in large GWAS on age at VB significantly associate with age at testicular growth and pubic hair development, suggesting that these events share a genetic architecture across ethnically distinct populations.",
author = "Lardone, {Mar{\'i}a C} and Busch, {Alexander S} and Santos, {Jos{\'e} L} and Patricio Miranda and Susana Eyheramendy and Ana Pereira and Anders Juul and Kristian Almstrup and Ver{\'o}nica Mericq",
note = "{\circledC} Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2020",
month = "3",
day = "1",
doi = "10.1210/clinem/dgaa003",
language = "English",
volume = "105",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The/Endocrine Society",
number = "3",

}

RIS

TY - JOUR

T1 - A Polygenic Risk Score Suggests Shared Genetic Architecture of Voice Break With Early Markers of Pubertal Onset in Boys

AU - Lardone, María C

AU - Busch, Alexander S

AU - Santos, José L

AU - Miranda, Patricio

AU - Eyheramendy, Susana

AU - Pereira, Ana

AU - Juul, Anders

AU - Almstrup, Kristian

AU - Mericq, Verónica

N1 - © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2020/3/1

Y1 - 2020/3/1

N2 - CONTEXT: Voice break, as a landmark of advanced male puberty in genome-wide association studies (GWAS), has revealed that pubertal timing is a highly polygenic trait. Although voice break is easily recorded in large cohorts, it holds quite low precision as a marker of puberty. In contrast, gonadarche and pubarche are early and clinically well-defined measures of puberty onset.OBJECTIVE: To determine whether a polygenic risk score (PRS) of alleles that confer risk for voice break associates with age at gonadarche (AAG) and age at pubarche (AAP) in Chilean boys.EXPERIMENTAL DESIGN: Longitudinal study.SUBJECTS AND METHODS: 401 boys from the Growth and Obesity Chilean Cohort Study (n = 1194; 49.2% boys).MAIN OUTCOME MEASURES: Biannual clinical pubertal staging including orchidometry. AAG and AAP were estimated by censoring methods. Genotyping was performed using the Multi-Ethnic Global Array (Illumina). Using GWAS summary statistics from the UK-Biobank, 29 significant and independent single nucleotide polymorphisms associated with age at voice break were extracted. Individual PRS were computed as the sum of risk alleles weighted by the effect size.RESULTS: The PRS was associated with AAG (β=0.01, P = 0.04) and AAP (β=0.185, P = 0.0004). In addition, boys within the 20% highest PRS experienced gonadarche and pubarche 0.55 and 0.67 years later than those in the lowest 20%, respectively (P = 0.013 and P = 0.007).CONCLUSIONS: Genetic variants identified in large GWAS on age at VB significantly associate with age at testicular growth and pubic hair development, suggesting that these events share a genetic architecture across ethnically distinct populations.

AB - CONTEXT: Voice break, as a landmark of advanced male puberty in genome-wide association studies (GWAS), has revealed that pubertal timing is a highly polygenic trait. Although voice break is easily recorded in large cohorts, it holds quite low precision as a marker of puberty. In contrast, gonadarche and pubarche are early and clinically well-defined measures of puberty onset.OBJECTIVE: To determine whether a polygenic risk score (PRS) of alleles that confer risk for voice break associates with age at gonadarche (AAG) and age at pubarche (AAP) in Chilean boys.EXPERIMENTAL DESIGN: Longitudinal study.SUBJECTS AND METHODS: 401 boys from the Growth and Obesity Chilean Cohort Study (n = 1194; 49.2% boys).MAIN OUTCOME MEASURES: Biannual clinical pubertal staging including orchidometry. AAG and AAP were estimated by censoring methods. Genotyping was performed using the Multi-Ethnic Global Array (Illumina). Using GWAS summary statistics from the UK-Biobank, 29 significant and independent single nucleotide polymorphisms associated with age at voice break were extracted. Individual PRS were computed as the sum of risk alleles weighted by the effect size.RESULTS: The PRS was associated with AAG (β=0.01, P = 0.04) and AAP (β=0.185, P = 0.0004). In addition, boys within the 20% highest PRS experienced gonadarche and pubarche 0.55 and 0.67 years later than those in the lowest 20%, respectively (P = 0.013 and P = 0.007).CONCLUSIONS: Genetic variants identified in large GWAS on age at VB significantly associate with age at testicular growth and pubic hair development, suggesting that these events share a genetic architecture across ethnically distinct populations.

U2 - 10.1210/clinem/dgaa003

DO - 10.1210/clinem/dgaa003

M3 - Journal article

VL - 105

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -

ID: 59383658