期刊
BIPOLAR DISORDERS
卷 17, 期 8, 页码 859-868出版社
WILEY
DOI: 10.1111/bdi.12347
关键词
bipolar disorder; cognition; dopamine function hypothesis; single nucleotide polymorphisms
资金
- Swedish Medical Research Council [K2014-62X-14647-12-51, K2010-61P-21568-01-4]
- Swedish foundation for Strategic Research
- Swedish Brain foundation
- Swedish Federal Government under LUA/ALF [ALF 20130032, ALFGBG-142041]
- Psychiatric foundation
- Fredrik and Ingrid Thuring Foundation
ObjectivesLIM homeobox transcription factor 1, alpha (LMX1A) and neuregulin 1 (NRG1) are susceptibility genes for schizophrenia that have been implicated in the dopaminergic pathway and have been associated with altered cognitive functioning. We hypothesized that single nucleotide polymorphisms (SNPs) in LMX1A and NRG1 would be associated with cognitive functioning in bipolar disorder. MethodsIn total, four SNPs were directly genotyped. Regression models with five aggregated cognitive domains and intelligence quotient (IQ) score were run using risk variants of LMX1A (rs11809911, rs4657412, rs6668493) and NRG1 (rs35753505) as predictors. Models were performed in a clinical sample of patients with bipolar disorder (n = 114) and healthy controls (n = 104). ResultsThe risk variants of the rs11809911 SNP in LMX1A were negatively associated with IQ score and memory/learning, whereas the risk variants of rs35753505 in NRG1 were positively associated with IQ score (adjusted R-2 = 0.17, Q = 0.006) and memory/learning (adjusted R-2 = 0.24, Q = 0.001). The risk variants of the rs35753505 SNP in NRG1 were positively associated with language (adjusted R-2 = 0.11, Q = 0.006), visuospatial functions (adjusted R-2 = 0.23, Q = 0.001), and attention/speed (adjusted R-2 = 0.25, Q = 0.001). Results could not be replicated in controls. ConclusionsThe risk variants of the rs35753505 SNP were associated with increased performance in several cognitive domains and IQ, whereas the risk variants of the rs11809911 SNP in LMX1A was associated with reduced IQ and memory/learning.
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