Genetics of emotional reactivity in bipolar disorders.
BACKGROUND
Emotional reactivity has been proposed as a relevant intermediate phenotype of bipolar disorder (BD). Our goal was to identify genetic factors underlying emotional reactivity in a sample of bipolar patients.


METHODS
Affect intensity (a proxy measure of emotional reactivity) was measured in a sample of 281 euthymic patients meeting DSM-IV criteria for BD. We use a validated dimensional tool, the 40-item self-report Affect Intensity Measure scale developed by Larsen and Diener. Patients with BD were genotyped for 475. 740 SNPs (using Illumina HumanHap550 Beadchips or HumanHap610 Quad chip). Association was investigated with a general mixed regression model of the continuous trait against genotypes, including gender as covariate.


RESULTS
Four regions (1p31.3, 3q13.11, 11p15.1 and 11q14.4) with a p-value lower or equal to 5×10(-6) were identified. In these regions, the joint effect of the four variants accounted for 24.5% of the variance of AIM score. Epistasis analysis did not detect interaction between these variants. In the 11p15.1 region, the rs10766743 located in the intron of the NELL1 gene remained significant after correction for multiple testing (p=2×10(-7)).


CONCLUSIONS
These findings illustrate that focusing on quantitative intermediate phenotypes can facilitate the identification of genetic susceptibility variants in BD.
Inserm, UMRS-958, Paris, France; Université Paris-Diderot, Sorbonne Paris Cité, Paris, France. Electronic address: flavie.mathieu@inserm.fr.
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Mathieu
INSERM U955, Equipe de Psychiatrie Translationelle, Créteil, France; Université Paris Est, Faculté de Médecine, Créteil, France; AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, Créteil, France; Fondation FondaMental, Créteil, France.
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Etain
Université Paris-Diderot, Sorbonne Paris Cité, Paris, France; INSERM, UMR-S946, Paris, France.
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Dizier
INSERM U955, Equipe de Psychiatrie Translationelle, Créteil, France.
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Lajnef
Commissariat à l'Energie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France.
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Lathrop
AP-HP, Groupe Hospitalier Henri Mondor, Plateforme de Ressources Biologiques Centre d'Investigation Clinique, Créteil F-94000, France; AP-HP, Groupe Hospitalier Saint-Louis, Lariboisière, F. Widal, Service de Psychiatrie, Paris; INSERM U955, Equipe de Psychiatrie Translationelle, Créteil, France.
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Cabon
INSERM U955, Equipe de Psychiatrie Translationelle, Créteil, France; Université Paris Est, Faculté de Médecine, Créteil, France; AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, Créteil, France; Fondation FondaMental, Créteil, France.
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Leboyer
INSERM U955, Equipe de Psychiatrie Translationelle, Créteil, France; Université Paris Est, Faculté de Médecine, Créteil, France; AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, Créteil, France; Fondation FondaMental, Créteil, France.
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Henry
Université Paris-Diderot, Sorbonne Paris Cité, Paris, France; Fondation FondaMental, Créteil, France; INSERM UMR-S1144, Paris, France.
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Bellivier
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
Affect intensity; Association study – gene–gene interaction; Bipolar disorder; Intermediate phenotype