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Polymorphisms of dopamine pathway genes NRG 1 and LMX 1A are associated with cognitive performance in bipolar disorder
Author(s) -
Rolstad Sindre,
Pålsson Erik,
Ekman Carl Johan,
Eriksson Elias,
Sellgren Carl,
Landén Mikael
Publication year - 2015
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1111/bdi.12347
Subject(s) - single nucleotide polymorphism , snp , psychology , cognition , dopaminergic , bipolar disorder , neuregulin 1 , clinical psychology , genetics , oncology , psychiatry , neuroscience , gene , dopamine , genotype , medicine , biology
Objectives LIM homeobox transcription factor 1, alpha ( LMX 1A ) and neuregulin 1 ( NRG 1 ) 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 ( SNP s) in LMX 1A and NRG 1 would be associated with cognitive functioning in bipolar disorder. Methods In total, four SNP s were directly genotyped. Regression models with five aggregated cognitive domains and intelligence quotient ( IQ ) score were run using risk variants of LMX 1A (rs11809911, rs4657412, rs6668493) and NRG 1 (rs35753505) as predictors. Models were performed in a clinical sample of patients with bipolar disorder (n = 114) and healthy controls (n = 104). Results The risk variants of the rs11809911 SNP in LMX 1A were negatively associated with IQ score and memory/learning, whereas the risk variants of rs35753505 in NRG 1 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 NRG 1 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. Conclusions The 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 LMX 1A was associated with reduced IQ and memory/learning.