Family-based genome-wide association analysis of novelty seeking in a Korean schizophrenic population: A pilot study

Schizophrenia (SPR) is the most devastating mental illness that causes severe deterioration in social and occupational functioning, but, the etiology remains unknown. The objective of this study is to explore the genetic underpinnings of novelty seeking behavior in schizophrenic family within the Korean population. By conducting a family-based genome-wide association study, we aim to identify potential genetic markers and variations associated with novelty seeking traits in the context of SPR. 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 analyzed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test (qFAM) was used to derive SNP association values across all chromosomes. Although none of the final 800,000 SNPs reached the genome-wide significant threshold of 8.45 × 10-7, the most significant 4 SNPs were within the 10-5 to 10-7. This study identifies genetic associations between novelty seeking behavior and SPR within families. RAPGEF5 emerges as a significant gene, along with other neuropsychiatric-related genes. Noteworthy genes like DRD4 and COMT did not show associations, possibly due to the focus on schizophrenic family. While shedding light on this complex relationship, larger studies are needed for robust conclusions and deeper mechanistic insights.