Common polygenic variation and risk for childhood-onset schizophrenia

Abstract

Childhood-onset schizophrenia (COS) is a rare and severe form of the disorder, with more striking abnormalities with respect to prepsychotic developmental disorders and abnormities in the brain development compared with later-onset schizophrenia. We previously documented that COS patients, compared with their healthy siblings and with adult-onset patients (AOS), carry significantly more rare chromosomal copy number variations, spanning large genomic regions (4100 kb) (Ahn et al. 2014). Here, we interrogated the contribution of common polygenic variation to the genetic susceptibility for schizophrenia. We examined the association between a direct measure of genetic risk of schizophrenia in 130 COS probands and 103 healthy siblings. Using data from the schizophrenia and autism GWAS of the Psychiatric Genomic Consortia, we selected three risk-related sets of single nucleotide polymorphisms from which we conducted polygenic risk score comparisons for COS probands and their healthy siblings. COS probands had higher genetic risk scores of both schizophrenia and autism than their siblings (P o 0.05). Given the small sample size, these findings suggest that COS patients have more salient genetic risk than do AOS.

Whole-Genome Sequencing and Integrative Genomic Analysis Approach on Two 22q11.2 Deletion Syndrome Family Trios for Genotype to Phenotype Correlations

“…For example, the top four prioritized coding target genes ( NTRK2 , RELN , HDAC1 , and KIF5C ) have been previously associated with cognitive disorders or psychiatric illness, including SCZD [Sharma et al., ; Otnaess et al., ; Ovadia and Shifman, ; Bergen et al., ]. As a whole, we identified an enrichment of SCZD candidate genes in P1 compared with P2, which is in line with recent studies on SCZD, showing that affected individuals have increased burden of genetic variants [Ahn et al., ; Chan, et al. ; Kong et al., ].…”

Polygenic Scores in Epidemiology: Risk Prediction, Etiology, and Clinical Utility

“…This approach holds incredible promise for aiding in the categorizing of specific phenotypic or risk subgroups, for example, among those with PGS in upper and lower quantiles. Recently these methods have been applied to identify individuals at high risk for early disease onset 34, 35 , those likely to suffer from comorbid disorders 36, 37 , those with treatment resistant disease 38 , those likely to benefit from intervention 39 and those who are more likely to suffer from more severe chronic disease 40 . PGS methods will continue to be actively used in research settings to identify phenotypically interesting or unique case subsets.…”

Polygenic risk scores distinguish patients from non‐affected adult relatives and from normal controls in schizophrenia and bipolar disorder multi‐affected kindreds

“…Another study tried to identify brain regions whose function may be related to BD PRS and also examined the discrimination by the BD PRS of BD patients from unaffected first‐degree relative and unrelated healthy controls (Dima, de Jong, Breen, & Frangou, ), but the group sizes were small. A study of Ahn, An, Shugart, and Rapoport () also found that childhood‐onset SZ patients had higher genetic risk scores for SZ than their healthy siblings with a SZ PRS defined from the PGC results.…”