Common variant at 16p11.2 conferring risk of psychosis
2014
Epidemiological and genetic data support the notion that schizophrenia and
bipolar disordershare genetic risk factors. In our previous
genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and
bipolar disorder(
psychosis) phenotype (addition of 7469
bipolar disordercases, 1535 schizophrenia cases, 333 other
psychosiscases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of
psychosiswhen duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).
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