Browsing by Author "Miranda, José Patricio"

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    A Polygenic Risk Score Suggests Shared Genetic Architecture of Voice Break With Early Markers of Pubertal Onset in Boys
    (2020) Lardone, María C.; Busch, Alexander S.; Santos Martín, José Luis; Miranda, José Patricio; Eyheramendy Duerr, Susana; Pereira, Ana; Juul, Anders; Almstrup, Kristian; Mericq, Verónica; José Patricio, Miranda
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    Association between plasma leptin/adiponectin ratio and insulin resistance indexes in prepubertal children
    (2024) Bravo, Carolina; Mericq, Verónica; Pereira, Ana; Corvalán, Camila; Tobar, Hugo E.; Miranda, José Patricio; Santos, José Luis
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    Correction to: Novel loci and mapuche genetic ancestry are associated with pubertal growth traits in Chilean boys (Human Genetics, (2021), 10.1007/s00439-021-02290-3)
    (Springer Science and Business Media Deutschland GmbH, 2021) Vicuña, Lucas; Norambuena, Tomás; Miranda, José Patricio; Eyheramendy, Susana; Pereira, Ana; Mericq, Verónica; Ongaro, Linda; Montinaro, Francesco; Lorenzoni Santos, José Guillermo
    © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.Several typos were introduced in the original article and they have been corrected. The original article has been revised.
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    Genome-Wide Association Study and Polygenic Risk Scores of Serum DHEAS Levels in a Chilean Children Cohort
    (2021) Miranda, José Patricio
    Context 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.
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    Novel loci and mapuche genetic ancestry are associated with pubertal growth traits in Chilean boys
    (2021) Miranda, José Patricio
    Puberty is a complex developmental process that varies considerably among individuals and populations. Genetic factors explain a large proportion of the variability of several pubertal traits. Recent genome-wide association studies (GWAS) have identified hundreds of variants involved in traits that result from body growth, like adult height. However, they do not capture many genetic loci involved in growth changes over distinct growth phases. Further, such GWAS have been mostly performed in Europeans, but we do not know how these findings relate to other continental populations. In this study, we analyzed the genetic basis of three pubertal traits; namely, peak height velocity (PV), age at PV (APV) and height at APV (HAPV). We analyzed a cohort of 904 admixed Chilean children and adolescents with European and Mapuche Native American ancestries. Height was measured on roughly a 6-month basis from childhood to adolescence between 2006 and 2019. We predict that the difference in HAPV between an European and a Mapuche adolescent is 4.3 cm higher in the European (P = 0.042) and APV is 0.73 years later for the European compared with the Mapuche adolescent on average (P = 0.023). Further, by performing a GWAS on 774, 433 single-nucleotide polymorphisms, we identified a genetic signal harboring 3 linked variants significantly associated with PV in boys (P < 5 x 10(-8)). This signal has never been associated with growth-related traits.