Genome-Wide Association Study and Polygenic Risk Scores of Serum DHEAS Levels in a Chilean Children Cohort

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dc.contributor.authorMiranda, José Patricio
dc.date.accessioned2023-05-19T20:49:13Z
dc.date.available2023-05-19T20:49:13Z
dc.date.issued2021
dc.description.abstractContext Adrenarche reflects the developmental growth of the adrenal zona reticularis, which produces increasing adrenal androgen secretion (eg, dehydroepiandrosterone [DHEA]/dehydroepiandrosterone sulfate [DHEAS]) from approximately age 5 to 15 years. Objective We hypothesized that the study of the genetic determinants associated with variations in serum DHEAS during adrenarche might detect genetic variants influencing the rate or timing of this process. Methods Genome-wide genotyping was performed in participants of the Chilean pediatric Growth and Obesity Chilean Cohort Study (GOCS) cohort (n = 788). We evaluated the genetic determinants of DHEAS levels at the genome-wide level and in targeted genes associated with steroidogenesis. To corroborate our findings, we evaluated a polygenic risk score (PRS) for age at pubarche, based on the discovered variants, in children from the same cohort. Results We identified one significant variant at the genome-wide level in the full cohort, close to the GALR1 gene (P = 3.81 x 10(-8)). In addition, variants suggestive of association (P < 1 x 10(-5)) were observed in PRLR, PITX1, PTPRD, NR1H4, and BCL11B. Stratifying by sex, we found variants suggestive of association in SERBP1 and CAMTA1/VAMP3 for boys and near ZNF98, TRPC6, and SULT2A1 for girls. We also found significant reductions in age at pubarche in those children with higher PRS for greater DHEAS based on these newly identified variants. Conclusion Our results disclose one variant associated with DHEAS concentrations at the level of genome-wide association study significance, and several variants with a suggestive association that may be involved in the genetic regulation of adrenarche.
dc.fechaingreso.objetodigital2025-03-29
dc.fuente.origenORCID-mayo23
dc.identifier.doi10.1210/clinem/dgab814
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/70006
dc.identifier.wosidWOS:000773033100062
dc.issue.numeroNo. 4
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final1738
dc.pagina.inicio1727
dc.revistaJournal of Clinical Endocrinology & Metabolism
dc.rightsacceso abierto
dc.subject.ods05 Gender equality
dc.subject.ods03 Good health and well-being
dc.subject.odspa05 Igualdad de género
dc.subject.odspa03 Salud y bienestar
dc.titleGenome-Wide Association Study and Polygenic Risk Scores of Serum DHEAS Levels in a Chilean Children Cohort
dc.typeartículo
dc.volumenVol. 107
sipa.indexWOS
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