|Association between schizophrenia and common variation in neurocan (NCAN), a genetic risk factor for bipolar disorder.|
||Having the A allele at this SNP makes your risk for developing bipolar disorder or schizophrenia higher.
||Having any copies of A at this SNP heightens your risk for bipolar disorder and schizophrenia.
||Normal risk of bipolar disorder or schizophrenia
||Genome-wide Association Study Identifies Genetic Variation in Neurocan as a Susceptibility Factor for Bipolar Disorder
rs1064395 is a single nucleotide variant (SNV) found in the neurocan gene (NCAN) that has been implicated as a predictor of both bipolar disorder (BD) and schizophrenia. BD is characterized by a fluctuation between manic episodes and severe depression. Schizophrenia is characterized by hallucinations, both visual and auditory, paranoia, disorganized thinking and lack of normal social skills.
NCAN is a chondroitin sulfate proteoglycan that is involved in cell adhesion and migration. It contains 14 exons and spans 41 kb of the genome at the location 19p12. [OMIM] It has also been found that, in mice, this gene is expressed in a localized way in the cortical and hippocampal regions of the brain which are responsible for cognition and regulation of emotions. [21353194?dopt=Abstract PMID 21353194]
In 2011, a study by Cichon et al identified rs1064395 in a genome-wide association study (GWAS) for Bipolar Disorder (BD). This study was done by analyzing around 500,000 autosomal SNPs and 12,000 X-chromosomal SNPS in 682 patients with BD and 1300 controls. The patients studied were from Europe, the USA, and Australia. The study then went forward to test the top 48 hits from their initial GWAS with an independent cohort of 1729 cases and 2313 controls, which narrowed down their significant hits to a list of eight. These eight were then used in a meta analysis. The rs1064395 was highly significant with a p-value of 3.02X10-8 and an odds ratio of 1.31, with A being the risk allele. The authors then further validated with a much larger sample size (6030 cases and 31,749 controls) and found a p-value of 2.74X10-4 and an odds ratio of 1.12 which, combined with their previous study lead to an overall p-value of 2.14X10-9 and an odds ratio of 1.17. [21353194?dopt=Abstract PMID 21353194]
In 2012, a study by Mühleisen et al investigated this same SNP in case control studies involving schizophrenic patients. They designed a patient-control study using samples from patients with European ancestry. The initial study included a cohort of 5061 patients and 9655 controls. The risk A-allele was found more frequently in schizophrenic patients then in controls with a p-value of 2.28X10 -8 and an odds ratio of 1.11. They followed up this initial experiment using a independent cohort from the Schizophrenia Psychiatric GWAS Consortium that included 5537 patients and 8043 controls. This follow up inquiry yielded a p-value of 0.0239 and an odds ratio of 1.07. Thus, these authors concluded that, not only is rs1064395 predictive of BD, it is also predictive of schizophrenia. [PMID 22497794]
[PMID 22005930] Genome-wide association study of Alzheimer's disease with psychotic symptoms.
[PMID 25220293] A genome-wide supported psychiatric risk variant in NCAN influences brain function and cognitive performance in healthy subjects
[PMID 25801500] NCAN Cross-Disorder Risk Variant is Associated with Limbic Gray Matter Deficits in Healthy Subjects and Major Depression