Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia.

ABSTRACT: By analyzing the exomes of 12,332 unrelated Swedish individuals, including 4,877 individuals affected with schizophrenia, in ways informed by exome sequences from 45,376 other individuals, we identified 244,246 coding-sequence and splice-site ultra-rare variants (URVs) that were unique to individual Swedes. We found that gene-disruptive and putatively protein-damaging URVs (but not synonymous URVs) were more abundant among individuals with schizophrenia than among controls (P = 1.3 × 10^-10). This elevation of protein-compromising URVs was several times larger than an analogously elevated rate for de novo mutations, suggesting that most rare-variant effects on schizophrenia risk are inherited. Among individuals with schizophrenia, the elevated frequency of protein-compromising UR

SUBMITTER: Genovese G 

PROVIDER: S-EPMC5104192 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature