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Personne :
Paccalet, Thomas

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Paccalet

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Thomas

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Université Laval

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ncf10904873

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  • PublicationAccès libre
    A multimodal attempt to follow-up linkage regions using RNA expression, SNPs and CpG methylation in schizophrenia and bipolar disorder kindreds
    (European Society of Human Genetics, 2019-11-06) Croteau, Jordie; Chagnon, Yvon C.; Paccalet, Thomas; Roy, Marc-André; Fournier, Alain; Bureau, Alexandre; Maziade, Michel
    The complexity of schizophrenia (SZ) and bipolar disorder (BD) has slowed down progress in understanding their genetic roots. Alternative genomic approaches are needed to bypass these difficulties. We attempted a multimodal approach to follow-up on reported linkage findings in SZ and BD from the Eastern Quebec kindreds in chromosomes 3q21, 4p34, 6p22, 8p21, 8p11, 13q11-q14, 15q13, 16p12, and 18q21. First, in 498 subjects, we measured RNA expression (47 K Illumina chips) in SZ and BD patients that we compared with their non-affected relatives (NARs) to identify, for each chromosomal region, genes showing the most significant differences in expression. Second, we performed SNP genotyping (700 K Illumina chips) and cis-eQTN analysis. Third, we measured DNA methylation on genes with RNA expression differences or eQTNs. We found a significant overexpression of the gene ITGB5 at 3q25 in SZ and BD after multiple testing p value adjustment. SPCS3 gene at 4q34, and FZD3 gene at 8p21, contained significant eQTNs after multiple testing corrections, while ITGB5 provided suggestive results. Methylation in associated genes did not explain the expression differences between patients and NARs. Our multimodal approach involving RNA expression, dense SNP genotyping and eQTN analyses, restricted to chromosomal regions having shown linkage, lowered the multiple testing burden and allowed for a deeper examination of candidate genes in SZ or BD.
  • PublicationAccès libre
    Polygenic risk scores distinguish patients from non-affected adult relatives and from normal controls in Schizophrenia and Bipolar Disorder multi-affected kindreds
    (Wiley, 2017-11-28) Mérette, Chantal; Boies, Sébastien; Paccalet, Thomas; Bureau, Alexandre; Maziade, Michel
    Recent studies have used results on SNP association with schizophrenia (SZ) and bipolar disorder (BD) to create polygenic risk scores (PRS) discriminating non‐familial unrelated patients from controls. Little is known about the role of PRS in densely affected multigenerational families. We tested PRS differences between affected SZ and BD family members from their non‐affected adult relatives (NAARs) in Eastern Quebec Kindreds and from controls. We examined 1227 subjects: from 17 SZ and BD kindreds, we studied 153 patients (57 SZ, 13 schizoaffective, and 83 BD) and 180 NAARs, and 894 unrelated controls from the Eastern Quebec population. PRS were derived from published case‐control association studies of SZ and BD. We also constructed a combined SZ and BD PRS by using SNPs from both SZ and BD PRS. SZ patients had higher SZ PRS than controls (p = 0.0039, R2 = 0.027) and BD patients had higher BD PRS than controls (p = 0.013, R2 = 0.027). Differences between affected subjects and NAARs and controls were significant with both SZ and BD PRS. Moreover, a combined SZ‐BD PRS was also significantly associated with SZ and BD when compared to NAARs (p = 0.0019, R2 = 0.010) and controls (p = 0.0025, R2 = 0.028), revealing a SZ‐BD commonality effect in PRS at the diagnosis level. The SZ and the BD PRS, however, showed a degree of specificity regarding thought disorder symptoms. Overall, our report would confirm the usefulness of PRS in capturing the contribution of common genetic variants to the risk of SZ and BD in densely affected families.