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Ulcerative colitis is under dual (mitochondrial and nuclear) genetic control

2016Journal article Open access
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dc.contributor.authorRosa, Alexandra
dc.contributor.authorAbrantes, Patrícia
dc.contributor.authorSousa, Inês
dc.contributor.authorFrancisco, Vânia
dc.contributor.authorSantos, Patrícia
dc.contributor.authorFrancisco, David
dc.contributor.authorXavier, Joana M.
dc.contributor.authorOliveira, Sofia A.
dc.date.accessioned2022-03-04T10:27:26Z
dc.date.available2022-03-04T10:27:26Z
dc.date.issued2016
dc.description.abstractBackground: Cellular oxidative stress and genetic susceptibility have been implicated in the multifactorial etiology of ulcerative colitis (UC). The nuclear genome association with UC has been intensely investigated, but the role of the mitochondrial DNA (mtDNA) has received far less attention and may account for part of the missing heritability. This study is a comprehensive analysis of the mtDNA contribution to UC susceptibility. Methods: The association of mitochondrial single-nucleotide polymorphisms (mtSNPs) and haplogroups with UC was tested in 488 cases and 833 controls of European ancestry from the NIDDK IBD Genetics Consortium Ulcerative Colitis Genome-Wide Association Study available through dbGaP and from the Illumina Genotype Control Database (studies 64 and 65). Results: No evidence of population stratification could be detected using 218 ancestry informative markers for European Americans. Seven of the 58 tested mtSNPs were nominally associated with UC, and A10550G in MT-ND4L withstands the Bonferroni correction (P ¼ 1.29E-06, odds ratio [ORG] [95% confidence interval (CI)] ¼ 4.80 [2.54–9.05], 10550G allele: 8.1% of patients and 1.9% of controls). A10550G remains equally associated after conditional analyses on the 11 UC genome-wide association studies (GWAS) top SNPs (6.35E-07 , Pcond , 4.58E-06), which suggests that it constitutes an independent risk factor from nuclear-encoded susceptibility loci. We detected additive (but not multiplicative) epistatic interactions between A10550G and all 11 top GWAS hits. Subhaplogroup K1 (P ¼ 0.021, OR [95% CI] ¼ 1.71 [1.08–2.69]) increased the risk for UC, whereas the U5b lineage conferred protection (P ¼ 0.016, OR [95% CI] ¼ 0.34 [0.14–0.82]). Conclusions: These results suggest that UC has a dual mitochondrial and nuclear genetic control that warrants further replication in independent data sets and reinforces its etiopathogenic complexity.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationRosa, A., Abrantes, P., Sousa, I., Francisco, V., Santos, P., Francisco, D., ... & Oliveira, S. A. (2016). Ulcerative colitis is under dual (mitochondrial and nuclear) genetic control. Inflammatory Bowel Diseases, 22(4), 774-781. https://doi.org/10.1097/MIB.0000000000000694pt_PT
dc.identifier.doi10.1097/MIB.0000000000000694pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.13/4114
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherOxford University Presspt_PT
dc.relationPatients as Health Care Innovators: An Empirical Investigation of Treatment, Therapies and Medical Devices (TT&MD) developed by Patients of Chronic Diseases
dc.relationGENETICS OF INTRACRANIAL ANEURYSMS: FROM ANIMAL MODEL TO HUMANS
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectUlcerative colitispt_PT
dc.subjectMitochondrial DNApt_PT
dc.subjectSingle-nucleotide polymorphismpt_PT
dc.subjectGenetic association studiespt_PT
dc.subjectGenetic predisposition to diseasept_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências da Vidapt_PT
dc.titleUlcerative colitis is under dual (mitochondrial and nuclear) genetic controlpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePatients as Health Care Innovators: An Empirical Investigation of Treatment, Therapies and Medical Devices (TT&MD) developed by Patients of Chronic Diseases
oaire.awardTitleGENETICS OF INTRACRANIAL ANEURYSMS: FROM ANIMAL MODEL TO HUMANS
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FIIM-GES%2F5015%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5665-PICT/CMUP-ERI%2FTPE%2F0028%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F35737%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F70008%2F2010/PT
oaire.citation.endPage781pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage774pt_PT
oaire.citation.titleInflammatory Bowel Diseasespt_PT
oaire.citation.volume22pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream5665-PICT
oaire.fundingStreamSFRH
person.familyNameda Silva Rosa
person.givenNamePatrícia Alexandra
person.identifier.ciencia-idF01B-3B5B-2269
person.identifier.orcid0000-0002-1827-6828
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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