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Mitochondrial GWAS and association of nuclear – mitochondrial epistasis with BMI in T1DM patients

dc.contributor.authorLudwig-Słomczyńska, Agnieszka H.
dc.contributor.authorSeweryn, Michał T.
dc.contributor.authorKapusta, Przemysław
dc.contributor.authorPitera, Ewelina
dc.contributor.authorHandelman, Samuel K.
dc.contributor.authorMantaj, Urszula
dc.contributor.authorCyganek, Katarzyna
dc.contributor.authorGutaj, Paweł
dc.contributor.authorDobrucka, Łucja
dc.contributor.authorWender-Ożegowska, Ewa
dc.contributor.authorMałecki, Maciej T.
dc.contributor.authorWołkow, Paweł P.
dc.date.accessioned2022-08-10T18:20:52Z
dc.date.available2022-08-10T18:20:52Z
dc.date.issued2020-07-07
dc.identifier.citationBMC Medical Genomics. 2020 Jul 07;13(1):97
dc.identifier.urihttps://doi.org/10.1186/s12920-020-00752-7
dc.identifier.urihttps://hdl.handle.net/2027.42/173678en
dc.description.abstractAbstract Background BMI is a strong indicator of complications from type I diabetes, especially under intensive treatment. Methods We have genotyped 435 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays and performed mitoGWAS on BMI. We identified additive interactions between mitochondrial and nuclear variants in genes associated with mitochondrial functioning MitoCarta2.0 and confirmed and refined the results on external cohorts: the Framingham Heart Study (FHS) and GTEx data. Linear mixed model analysis was performed using the GENESIS package in R/Bioconductor. Results We find a borderline significant association between the mitochondrial variant rs28357980, localized to MT-ND2, and BMI (β = − 0.69, p = 0.056). This BMI association was confirmed on 1889 patients from FHS cohort (β = − 0.312, p = 0.047). Next, we searched for additive interactions between mitochondrial and nuclear variants. MT-ND2 variants interacted with variants in the genes SIRT3, ATP5B, CYCS, TFB2M and POLRMT. TFB2M is a mitochondrial transcription factor and together with TFAM creates a transcription promoter complex for the mitochondrial polymerase POLRMT. We have found an interaction between rs3021088 in MT-ND2 and rs6701836 in TFB2M leading to BMI decrease (inter_pval = 0.0241), while interaction of rs3021088 in MT-ND2 and rs41542013 in POLRMT led to BMI increase (inter_pval = 0.0004). The influence of these interactions on BMI was confirmed in external cohorts. Conclusions Here, we have shown that variants in the mitochondrial genome as well as additive interactions between mitochondrial and nuclear SNPs influence BMI in T1DM and general cohorts.
dc.titleMitochondrial GWAS and association of nuclear – mitochondrial epistasis with BMI in T1DM patients
dc.typeJournal Article
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/173678/1/12920_2020_Article_752.pdf
dc.identifier.doihttps://dx.doi.org/10.7302/5409
dc.language.rfc3066en
dc.rights.holderThe Author(s)
dc.date.updated2022-08-10T18:20:51Z
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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