Increased Rare Variants in Schizophrenia Patients Linked to DISC1 Pathway Genes
Author Information
Author(s): Moens Lotte N., De Rijk Peter, Reumers Joke, Van Den Bossche Maarten J. A., Glassee Wim, De Zutter Sonia, Lenaerts An-Sofie, Nordin Annelie, Nilsson Lars-Göran, Medina Castello Ignacio, Norrback Karl-Fredrik, Goossens Dirk, Van Steen Kristel, Adolfsson Rolf, Del-Favero Jurgen
Primary Institution: Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium
Hypothesis
The study investigates the contribution of genetic variation in DISC1 and its interaction partners to schizophrenia susceptibility.
Conclusion
The study found that rare missense variants in the DISC1 pathway are more prevalent in schizophrenia patients, particularly in those with early onset.
Supporting Evidence
- Non-synonymous rare variants with a MAF<0.01 were significantly more present in patients compared to controls (8.64% versus 4.7%).
- The increased burden of rare missense variants was particularly pronounced in early onset patients (12.9% versus 4.7%).
- Approximately 90% of the identified missense variants reside in intrinsically disordered protein regions.
Takeaway
Researchers looked at genes related to schizophrenia and found that people with the illness have more rare gene changes than those without it, especially if they got sick young.
Methodology
The study used pooled sample 454 sequencing to analyze genetic variants in DISC1 and its interaction partners in schizophrenia patients and controls.
Potential Biases
Potential bias due to the isolated population and the focus on specific candidate genes.
Limitations
The study's findings may not be generalizable due to the specific population studied and the relatively small sample size for variant discovery.
Participant Demographics
486 unrelated schizophrenia patients and 514 unrelated control individuals from a northern Swedish population, predominantly Caucasian.
Statistical Information
P-Value
0.018
Confidence Interval
95% CI: 1.2–3.5
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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