Resequencing and association analysis of GAP43 with autism spectrum disorder and schizophrenia in a Japanese population. (April 2021)

• Record Type: Journal Article
• Authors: Arta, Reza K.; Watanabe, Yuichiro; Inoue, Emiko; Nawa, Yoshihiro; Morikawa, Ryo; Egawa, Jun; Kushima, Itaru; Igeta, Hirofumi; Hoya, Satoshi; Sugimoto, Atsunori; Tanra, Andi J.; Ozaki, Norio; Someya, Toshiyuki
• Is Part Of: Research in autism spectrum disorders. Volume 82(2021)
• Publication Date: 2021-04
• Subjects: Autism spectrum disorder -- GAP43 -- Japanese -- Schizophrenia; Autism spectrum disorders -- Periodicals; 616.85882005
• DOI: 10.1016/j.rasd.2021.101729
• Languages: English
• ISSNs: 1750-9467

Abstract

Highlights: The variant, GAP43 p.Asp59Gly, was identified in an ASD patient via resequencing. The variant was not associated with ASD or schizophrenia. Rare GAP43 variants may not contribute to ASD or schizophrenia susceptibility. Abstract: Background: Growth-associated protein 43 (GAP43), a synaptic protein involved in axonal growth and synaptic plasticity, is implicated in the pathophysiology of autism spectrum disorder (ASD) and schizophrenia. To examine the role of rare GAP43 variants in the genetic etiology of ASD and schizophrenia in a Japanese population, we performed resequencing and association analysis. Methods: First, we resequenced the GAP43 coding region in 295 ASD patients, 323 schizophrenia patients and 304 controls. Second, we genotyped rs561268447 in 273 ASD patients, 1, 150 schizophrenia patients and 1, 022 controls. Third, we performed an association analysis of rs561268447 in 568 ASD patients, 1, 473 schizophrenia patients and 10, 127 controls. Results: We identified a rare putatively damaging missense variant (rs561268447) in an ASD patient via resequencing. However, we did not detect the variant in 2, 445 individuals via genotyping. The variant was not significantly associated with ASD or schizophrenia in the association analysis. Conclusion: This study does not provide evidence for the contribution of rare GAP43 variants to ASD or schizophrenia susceptibility in the Japanese population.