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Polygenic risk scores in schizophrenia with clinically significant copy number variants
Author(s) -
Taniguchi Satoru,
Ninomiya Kohei,
Kushima Itaru,
Saito Takeo,
Shimasaki Ayu,
Sakusabe Takaya,
Momozawa Yukihide,
Kubo Michiaki,
Kamatani Yoichiro,
Ozaki Norio,
Ikeda Masashi,
Iwata Nakao
Publication year - 2020
Publication title -
psychiatry and clinical neurosciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 74
eISSN - 1440-1819
pISSN - 1323-1316
DOI - 10.1111/pcn.12926
Subject(s) - polygenic risk score , schizophrenia (object oriented programming) , copy number variation , psychology , clinical psychology , psychiatry , genetics , medicine , biology , gene , single nucleotide polymorphism , genotype , genome
Aims Recent studies have revealed that the interplay between polygenic risk scores (PRS) and large copy number variants (CNV; >500kb) is essential for the etiology of schizophrenia (SCZ). To replicate previous findings, including those for smaller CNV (>10kb), the PRS between SCZ patients with and without CNV were compared. Methods The PRS were calculated for 724 patients with SCZ and 1178 healthy controls (HC), genotyped using array‐based comparative genomic hybridization and single nucleotide polymorphisms chips, and comparisons were made between cases and HC, or between subjects with and without ‘clinically significant’ CNV. Results First, we replicated the higher PRS in patients with SCZ compared to that in HC (without taking into account the CNV). For clinically significant CNV, as defined by the American College of Medical Genetics (‘pathogenic’ and ‘uncertain clinical significance, likely pathogenic’ CNV), 66 patients with SCZ carried clinically significant CNV, whereas 658 SCZ patients had no such CNV. In the comparison of PRS between cases with/without the CNV, despite no significant difference in PRS, significant enrichment of the well‐established risk CNV (22q11.2 deletion and 47,XXY/47,XXX) was observed in the lowest decile of PRS in SCZ patients with the CNV. Conclusion Although the present study failed to replicate the significant difference in PRS between SCZ patients with and without clinically significant CNV, SCZ patients with well‐established risk CNV tended to have a lower PRS. Therefore, we speculate that the CNV in SCZ patients with lower PRS may contain ‘genuine’ risk; PRS is a possible tool for prioritizing clinically significant CNV because the power of the CNV association analysis is limited due to their rarity.