Genetic determinants of serum bilirubin using inferred native American gene variants in Chilean adolescents

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dc.article.number1382103
dc.catalogadorgjm
dc.contributor.authorMiranda Marín, José Patricio
dc.contributor.authorPereira, Ana
dc.contributor.authorCorvalán, Camila
dc.contributor.authorMiquel P., Juan Francisco
dc.contributor.authorAlberti, Gigliola
dc.contributor.authorGana Ansaldo, Juan Cristóbal
dc.contributor.authorSantos Martín, José Luis
dc.date.accessioned2024-07-18T20:27:31Z
dc.date.available2024-07-18T20:27:31Z
dc.date.issued2024
dc.description.abstractGene variants in the UGT1A1 gene are strongly associated with circulating bilirubin levels in several populations, as well as other variants of modest effect across the genome. However, the effects of such variants are unknown regarding the Native American ancestry of the admixed Latino population. Our objective was to assess the Native American genetic determinants of serum bilirubin in Chilean admixed adolescents using the local ancestry deconvolution approach. We measured total serum bilirubin levels in 707 adolescents of the Chilean Growth and Obesity Cohort Study (GOCS) and performed high-density genotyping using the Illumina-MEGA array (>1.7 million genotypes). We constructed a local ancestry reference panel with participants from the 1000 Genomes Project, the Human Genome Diversity Project, and our GOCS cohort. Then, we inferred and isolated haplotype tracts of Native American, European, or African origin to perform genome-wide association studies. In the whole cohort, the rs887829 variant and others near UGT1A1 were the unique signals achieving genome-wide statistical significance (b = 0.30; p = 3.34 × 10−57). After applying deconvolution methods, we found that significance is also maintained in Native American (b = 0.35; p = 3.29 × 10−17) and European (b = 0.28; p = 1.14 × 10−23) ancestry components. The rs887829 variant explained a higher percentage of the variance of bilirubin in the Native American (37.6%) compared to European ancestry (28.4%). In Native American ancestry, carriers of the TT genotype of this variant averaged 4-fold higher bilirubinemia compared to the CC genotype (p = 2.82 × 10−12). We showed for the first time that UGT1A1 variants are the primary determinant of bilirubin levels in Native American ancestry, confirming its pan-ethnic relevance. Our study illustrates the general value of the local ancestry deconvolution approach to assessing isolated ancestry effects in admixed populations.
dc.description.funderComisión Nacional de Investigación Científica y Tecnológica de Chile CONICYT
dc.description.funderISCIII
dc.description.funderAgencia Nacional de Investigación y Desarrollo de Chile ANID
dc.description.funderERDF
dc.description.funderFONDECYT
dc.description.funderSpanish National Cancer Research Centre
dc.fechaingreso.objetodigital2024-07-18
dc.format.extent12 páginas
dc.fuente.origenORCID
dc.identifier.doi10.3389/fgene.2024.1382103
dc.identifier.issn1664-8021
dc.identifier.scopusidSCOPUS_ID:85194864241
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/87132
dc.identifier.wosidWOS:001235828300001
dc.information.autorucEscuela de Medicina; Miranda Marín, José Patricio; 0000-0002-8270-1112; 1126717
dc.information.autorucEscuela de Medicina; Miquel P., Juan Francisco; 0000-0002-0526-4377; 72216
dc.information.autorucEscuela de Medicina; Alberti, Gigliola; 0000-0002-8540-1326; 167316
dc.information.autorucEscuela de Medicina; Gana Ansaldo, Juan Cristóbal; 0000-0002-0400-2164; 8726
dc.information.autorucEscuela de Medicina; Santos Martín, José Luis; 0000-0003-2895-0369; 1005923
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaFrontiers in Genetics
dc.rightsacceso abierto
dc.rights.licenseCC BY 4.0 ATTRIBUTION 4.0 INTERNATIONAL Deed
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBilirubin
dc.subjectGenetic epidemiology
dc.subjectGWAS
dc.subjectLocal ancestry deconvolution
dc.subjectNative American
dc.subjectPopulation genomics
dc.subjectUGT1A1
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleGenetic determinants of serum bilirubin using inferred native American gene variants in Chilean adolescents
dc.typeartículo
dc.volumen15
sipa.codpersvinculados1126717
sipa.codpersvinculados72216
sipa.codpersvinculados167316
sipa.codpersvinculados8726
sipa.codpersvinculados1005923
sipa.trazabilidadORCID;2024-07-15
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