Welcome to the UPF Digital Repository

Genome-Wide Association Study (GWAS) on Bilirubin Concentrations in Subjects with Metabolic Syndrome: Sex-Specific GWAS Analysis and Gene-Diet Interactions in a Mediterranean Population

Show simple item record

dc.contributor.author Coltell, Oscar
dc.contributor.author Asensio, Eva M.
dc.contributor.author Sorlí, J.V.
dc.contributor.author Barragán, Rocio
dc.contributor.author Fernández-Carrión, Rebeca
dc.contributor.author Portolés, Olga
dc.contributor.author Ortega-Azorín, Carolina
dc.contributor.author Martínez-LaCruz, Raul
dc.contributor.author González, José I.
dc.contributor.author Zanon-Moreno, Vicente
dc.contributor.author Gimenez-Alba, Ignacio
dc.contributor.author Ros, Emilio
dc.contributor.author Ordovás, José M.
dc.contributor.author Corella, Dolores
dc.date.accessioned 2019-06-25T07:44:51Z
dc.date.available 2019-06-25T07:44:51Z
dc.date.issued 2019
dc.identifier.citation Coltell O, Asensio EM, Sorlí JV, Barragán R, Fernández-Carrión R, Portolés O. et al. Genome-Wide Association Study (GWAS) on Bilirubin Concentrations in Subjects with Metabolic Syndrome: Sex-Specific GWAS Analysis and Gene-Diet Interactions in a Mediterranean Population. Nutrients. 2019 Jan 4;11(1). pii: E90. DOI: 10.3390/nu11010090
dc.identifier.issn 2072-6643
dc.identifier.uri http://hdl.handle.net/10230/41861
dc.description.abstract Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporating the gender perspective into nutritional genomics, our main aim was to carry out a GWAS on total serum bilirubin concentrations in a Mediterranean population with metabolic syndrome, stratified by sex. Our secondary aim was to explore, as a pilot study, the presence of gene-diet interactions at the GWAS level. We included 430 participants (188 men and 242 women, aged 55⁻75 years, and with metabolic syndrome) in the PREDIMED Plus-Valencia study. Global and sex-specific GWAS were undertaken to analyze associations and gene-diet interaction on total serum bilirubin. Adherence (low and high) to the Mediterranean diet (MedDiet) was analyzed as the dietary modulator. In the GWAS, we detected more than 55 SNPs associated with serum bilirubin at p < 5 × 10-8 (GWAS level). The top-ranked were four SNPs (rs4148325 (p = 9.25 × 10-24), rs4148324 (p = 9.48 × 10-24), rs6742078 (p = 1.29 × 10-23), rs887829 (p = 1.39 × 10-23), and the rs4148324 (p = 9.48 × 10-24)) in the UGT1A1 (UDP glucuronosyltransferase family 1 member A1) gene, which replicated previous findings revealing the UGT1A1 as the major locus. In the sex-specific GWAS, the top-ranked SNPs at the GWAS level were similar in men and women (the lead SNP was the rs4148324-UGT1A1 in both men (p = 4.77 × 10-11) and women (p = 2.15 × 10-14), which shows homogeneous genetic results for the major locus. There was more sex-specific heterogeneity for other minor genes associated at the suggestive level of GWAS significance (p < 1 × 10-5). We did not detect any gene-MedDiet interaction at p < 1 × 10-5 for the major genetic locus, but we detected some gene-MedDiet interactions with other genes at p < 1 × 10-5, and even at the GWAS level for the IL17B gene (p = 3.14 × 10-8). These interaction results, however, should be interpreted with caution due to our small sample size. In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher MDPI
dc.rights Copyright © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Genome-Wide Association Study (GWAS) on Bilirubin Concentrations in Subjects with Metabolic Syndrome: Sex-Specific GWAS Analysis and Gene-Diet Interactions in a Mediterranean Population
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3390/nu11010090
dc.subject.keyword GWAS
dc.subject.keyword Mediterranean
dc.subject.keyword UGT1A1
dc.subject.keyword Bilirubin
dc.subject.keyword Gene-diet interaction
dc.subject.keyword Sex-specific
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account

Statistics

Compliant to Partaking