Family Based Genome-Wide Association Analysis of Schizophrenia in a Korean Population: A Pilot Study
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Objectives: Schizophrenia (SPR) is the most devastating mental illness that causes severe deterioration in social and occupational functioning, but, the aetiology remains unknown. The aim was to identify patterns of association and segregation for genetic variants and to identify the genes and signalling pathways that determine the risk of developing SPR, through a family-based Genome-wide association study. Methods: We have recruited 27 probands(with SPR) with their parents and siblings whenever possible. DNA was extracted from blood sampling of 58 individuals in 27 families and analysed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test was used to derive SNP association values across all chromosomes. Results: Although none of the final 800,000 SNPs reached the genome-wide significant threshold of 5×10-8, the most significant 3 SNPs were within the 10-5-10-7. Conclusions: This confirms that SPR is not monogenic but results as a consequence of interactions between multiple host genes and possibly also environmental factors. The present approach provides novel insights into the mechanisms underlying SPR and raises the possibility of identifying individuals at risk of acquiring this condition. In this study, several possible susceptibility genes have been identified that are linked to a range of different pathways, which could reflect the mind-body interaction that is included in the psychiatric genomics consortium.
Abstract
Objectives: Schizophrenia (SPR) is the most devastating mental illness that causes severe deterioration in social and occupational functioning, but, the aetiology remains unknown. The aim was to identify patterns of association and segregation for genetic variants and to identify the genes and signalling pathways that determine the risk of developing SPR, through a family-based Genome-wide association study. Methods: We have recruited 27 probands(with SPR) with their parents and siblings whenever possible. DNA was extracted from blood sampling of 58 individuals in 27 families and analysed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test was used to derive SNP association values across all chromosomes. Results: Although none of the final 800,000 SNPs reached the genome-wide significant threshold of 5×10-8, the most significant 3 SNPs were within the 10-5-10-7. Conclusions: This confirms that SPR is not monogenic but results as a consequence of interactions between multiple host genes and possibly also environmental factors. The present approach provides novel insights into the mechanisms underlying SPR and raises the possibility of identifying individuals at risk of acquiring this condition. In this study, several possible susceptibility genes have been identified that are linked to a range of different pathways, which could reflect the mind-body interaction that is included in the psychiatric genomics consortium.
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