RESUMO
Genetic variants in ankyrin 3 (ANK3) have recently been shown to be associated with bipolar disorder (BD). We genotyped three ANK3 SNPs previously found to be associated with BD (rs10994336, rs1938526, and rs9804190) in a Scandinavian BD case-control sample (N = 854/2,614). Due to evidence of genetic overlap between BD and schizophrenia (SZ), we also genotyped these three SNPs in a Scandinavian SZ case-control sample (N = 1,073/2,919). Combining our Scandinavian samples with an Icelandic sample (N = 435 BD cases, 651 SZ cases, and 11,491 healthy controls), we found rs10994336 and rs9804190 to be nominally significantly associated with BD in this combined Nordic BD sample (N = 1,289/14,105). Nominal P was 0.015/0.018 (fixed/random effect) for rs10994336 (Bonferroni corrected P = 0.044/0.053) and 0.023 for rs9804190 (Bonferroni corrected P = 0.069). None of the SNPs were significantly associated with SZ in the combined Nordic SZ case-control sample (N = 1,724/14,410). These results further support that ANK3 is a susceptibility gene specific to BD and that more than one risk locus is involved.
Assuntos
Anquirinas/genética , Transtorno Bipolar/genética , Estudos de Associação Genética , Esquizofrenia/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Islândia , Masculino , Polimorfismo de Nucleotídeo Único , Países Escandinavos e NórdicosRESUMO
Individual variation in pharmacokinetics of psychotropic drugs, particularly metabolism, is an important factor to consider in pharmacological treatment in psychiatry. A large proportion of this variance is still not accounted for, but evidence so far suggests the involvement of genetic factors. We performed a genome-wide association study (GWAS) with concentration dose ratio (CDR) as sub-phenotype to assess metabolism rate of psychotropic drugs in a homogenous Norwegian sample of 1334 individuals diagnosed with a severe mental disorder. The GWAS revealed one genome-wide significant marker (rs16935279, p-value=3.95×10(-10), pperm=7.5×10(-4)) located in an intronic region of the lncRNA LOC100505718. Carriers of the minor allele have a lower metabolism rate of antiepileptic drugs compared to major allele carriers. In addition, several nominally significant associations between single nucleotide polymorphisms (SNPs) and CDR for antipsychotic, antidepressant and antiepileptic drugs were disclosed. We consider standardised CDR to be a useful measure of the metabolism rate of a drug. The present findings indicate that common gene variants could affect the metabolism of psychotropic drugs. This warrants further investigations into the functional mechanisms involved as it may lead to identification of predictive markers as well as novel drug targets.