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A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms
P A Holmans1, B Riley, A E Pulver
1Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK.
Molecular Psychiatry
|February 19, 2009
Summary
This study identified potential schizophrenia susceptibility loci on chromosomes 8p21, 10p12, and 22q11.1 using genomewide linkage analysis in large family sets. Further investigation is warranted to pinpoint specific genetic variations contributing to schizophrenia risk.
Area of Science:
- Genetics
- Psychiatry
- Genomics
Background:
- Schizophrenia is a complex psychiatric disorder with a significant genetic component.
- Identifying specific genetic loci is crucial for understanding disease mechanisms and developing targeted therapies.
Purpose of the Study:
- To conduct a genomewide linkage scan in informative schizophrenia families to identify chromosomal regions associated with the disorder.
- To investigate potential novel susceptibility loci for schizophrenia beyond known candidate genes.
Main Methods:
- Utilized multipoint linkage analysis with correction for marker-marker linkage disequilibrium on 5861 single nucleotide polymorphisms (SNPs).
- Analyzed data from 707 European-ancestry families (1615 affected, 1602 unaffected) and a total of 807 families (1900 affected, 1839 unaffected).
- Employed logistic regression allele-sharing analysis allowing for intersite heterogeneity.
Main Results:
- Suggestive linkage evidence observed on chromosomes 8p21, 8q24.1, 9q34, and 12q24.1 in European families.
- Genomewide significant evidence for linkage identified on chromosome 10p12.
- Significant heterogeneity noted on chromosome 22q11.1.
- Most consistent linkage evidence across analyses was on chromosome 8p21, with a region excluding the NRG1 gene.
Conclusions:
- The study identified several chromosomal regions, notably 8p21, 10p12, and 22q11.1, as potentially harboring schizophrenia susceptibility loci.
- The findings suggest the presence of one or more novel loci on chromosome 8p21, independent of the NRG1 gene.
- Consensus linkage regions identified in this study warrant further investigation using advanced genomic approaches to uncover causative variants.
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