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CURATOR
A pinboard by
Ali Bani-Fatemi

PhD student, University of Toronto

PINBOARD SUMMARY

I explore the efffect of the genome-wide significant risk alleles on age at onset in schizophrenia.

Schizophrenia is a debilitating disorder with high costs to society and a lifetime risk of around 1%. The age at onset (AAO) is a useful predictor for schizophrenia prognosis. Early onset schizophrenia, which has a higher genetic load, is more homogeneous and has been associated with lower cognitive development as compared to late onset schizophrenia. There is no consensus on the cut-off age for AAO; however, most studies arbitrarily assign the cut-off for early onset and late onset schizophrenia. Schizophrenia has a strong genetic component, with studies estimating 65-80% heritability. Both environmental and genetic factors may modulate risk for schizophrenia. This study explore the specific effect of the genetic risk markers on AAO. The main aim of this analysis is to highlight the risk markers and their associations with early onset schizophrenia, in order to restrict the list of genetic targets for biological validation and potential drug development. My sample consists of 167 Caucasian participants aged 18-75 years who were admitted to the Centre for Addiction and Mental Health (Toronto, Canada) in the schizophrenia program between 2011 and 2017. I used the gold standard tools to confirm the diagnosis of schizophrenia for all patients. Age at onset of psychosis was determined by the questionnaire administered to the patients during the interview. Blood was collected and DNA was extracted using a DNA blood kit (Qiagen, Germany). The DNA of the participants were genotyped for the DNA sequencing. I used specific computational program (PLINK) to analyze the genetic data and visualized the results in a commonly used bioinformatics software called Haploview. My results have not find support for any markers associated with AAO. Overall, this study may provide a methodology for future genetic analysis of schizophrenia and may also open a gateway for studies aiming at the biological validation of the known risk markers. This is a very unique area of research aiming to validate the schizophrenia risk variants to enhance drug discovery in schizophrenia.

1 ITEMS PINNED

Differential Allelic Expression of HTR1B in Suicide Victims: Genetic and Epigenetic Effect of the Cis-Acting Variants.

Abstract: In the present study, we tested the allelic imbalance of the C861G single nucleotide polymorphism (SNP) of HTR1B in the frontal cortex of suicide victims.The study was conducted using 3 sets of samples. First, C861G allele-specific mRNA levels in the frontal cortex were compared between suicide (n = 13) and nonsuicide controls (n = 13) from the Stanley Medical Research postmortem brain collection. Second, we tested common variants in the HTR1B promoter for linkage disequilibrium (LD) with the C861G variant in an unrelated sample of suicide attempters (SA; n = 38) and non-SA (NSA; n = 42). Finally, we performed a family-based association study of the C861G and promoter variants in 162 nuclear families using suicidal behavior severity scores as phenotype.We observed no alterations in the C/G expression ratio in suicide victims compared to nonsuicide controls (p = 0.370). When comparing the LD between the C861G and cis-acting SNPs, we did not find any differences in SA and NSA. There was no association between preferential transmission of cis-acting SNPs and suicidal behavior severity scores in both maternal and paternal meiosis.We found several promoter variants in LD that may potentially influence the allelic imbalance in the C861G variant. However, no evidence of allelic imbalance nor parent-of-origin effects of the C861G variant was observed in suicidal behavior. Further research is required to assess this marker in larger cohorts.

Pub.: 27 Apr '17, Pinned: 28 Aug '17