Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.

[Réception des Gueules cassées aveugles à l'Élysée le 22 mars 1920] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58515

Du Duel sous le rapport de la législation et des moeurs, suivi de l'ordonnance de Louis XIV, en 1651, du réquisitoire de M. Dupin, procureur général et de l'arrêt de la Cour de cassation du 22 juin 1837, par Augte Nougarède de Fayet,...

Comprend : Réquisitoire [22 juin 1837]

22/3/20, réception de soldats aveugles à l'Elysée : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58598

22/3/20, réception de soldats aveugles à l'Elysée : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58601

22/5/20, stade Jean Bouin, 41[e] R.I. contre 166[e] R.I. [match de football] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59351