Association between copy number variations in parkin (PRKN) and schizophrenia and autism spectrum disorder: A case–control study

• Published in: Neuropsychopharmacology reports 2024-03, Vol.44 (1), p.42-50
• Main Authors: Lo, Tzuyao, Kushima, Itaru, Kimura, Hiroki, Aleksic, Branko, Okada, Takashi, Kato, Hidekazu, Inada, Toshiya, Nawa, Yoshihiro, Torii, Youta, Yamamoto, Maeri, Kimura, Ryo, Funabiki, Yasuko, Kosaka, Hirotaka, Numata, Shusuke, Kasai, Kiyoto, Sasaki, Tsukasa, Yokoyama, Shigeru, Munesue, Toshio, Hashimoto, Ryota, Yasuda, Yuka, Fujimoto, Michiko, Usami, Masahide, Itokawa, Masanari, Arai, Makoto, Ohi, Kazutaka, Someya, Toshiyuki, Watanabe, Yuichiro, Egawa, Jun, Takahashi, Tsutomu, Suzuki, Michio, Yamasue, Hidenori, Iwata, Nakao, Ikeda, Masashi, Ozaki, Norio
• Format: Article
• Language: English
• Subjects: Algorithms; Autism; autism spectrum disorder; DNA copy number variations; Genomes; Genomics; Mental disorders; Original; parkin; Parkinson disease 2; Parkinson's disease; Pathogenesis; Schizophrenia
• ISSN: 2574-173X; 2574-173X
• DOI: 10.1002/npr2.12370

Aim The present study aimed to examine the association between copy number variations (CNVs) in parkin (PRKN) and schizophrenia (SCZ) and autism spectrum disorder (ASD) in a large case–control sample. Method Array comparative genomic hybridization was performed on 3111 cases with SCZ, 1236 cases with ASD, and 2713 controls. We systematically prioritized likely pathogenic CNVs (LP‐CNVs) in PRKN and examined their association with SCZ and ASD. Results In total, 3014 SCZ cases (96.9%), 1205 ASD cases (97.5%), and 2671 controls (98.5%) passed quality control. We found that monoallelic carriers of LP‐CNVs in PRKN were common (70/6890, 1.02%) and were not at higher risk of SCZ (p = 0.29) or ASD (p = 0.72). We observed that the distribution pattern of LP‐CNVs in the Japanese population was consistent with those in other populations. We also identified a patient diagnosed with SCZ and early‐onset Parkinson's disease carrying biallelic pathogenic CNVs in PRKN. The absence of Parkinson's symptoms in 10 other monoallelic carriers of the same pathogenic CNV further reflects the lack of effect of monoallelic pathogenic variants in PRKN in the absence of a second hit. Conclusion The present findings suggest that monoallelic CNVs in PRKN do not confer a significant risk for SCZ or ASD. However, further studies to investigate the association between biallelic CNVs in PRKN and SCZ and ASD are warranted. The study analyzed a large case–control sample of 3111 schizophrenia (SCZ) cases, 1236 autism spectrum disorder (ASD) cases, and 2713 controls to investigate the association between copy number variations (CNVs) in the parkin (PRKN) gene and neuropsychiatric disorders. The study found that monoallelic carriers of likely pathogenic CNVs in PRKN did not show a significant risk for SCZ or ASD. However, the study identified a patient with both SCZ and early‐onset Parkinson's disease who carries biallelic pathogenic CNVs in PRKN. This finding prompts further investigation into the relationship between biallelic CNVs in PRKN and the co‐occurrence of neuropsychiatric disorders.