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Identification of shared risk loci and pathways for bipolar disorder and schizophrenia

Forstner Andreas J., Hecker Julian, Hofmann Andrea, Maaser Anna, Reinbold Céline S., Mühleisen Thomas W., Leber Markus, Strohmaier Jana, Degenhardt Franziska, Treutlein Jens, Mattheisen Manuel, Schumacher Johannes, Streit Fabian, Meier Sandra, Herms Stefan, Hoffmann Per, Lacour André, Witt Stephanie H., Reif Andreas, Müller-Myhsok Bertram, Lucae Susanne, Maier Wolfgang, Schwarz Marcus, Vedder Helmut, Kammerer-Ciernioch Jutta, Pfennig Andrea, Bauer Michael, Hautzinger Martin, Moebus Susanne, Schenk Lorena M., Fischer Sascha B., Sivalingam Sugirthan, Czerski Piotr M., Hauser Joanna, Lissowska Jolanta, Szeszenia-Dabrowska Neonila, Brennan Paul, McKay James D., Wright Adam, Mitchell Philip B., Fullerton Janice M., Schofield Peter R., Montgomery Grant W., Medland Sarah E., Gordon Scott D., Martin Nicholas G., Krasnov Valery, Chuchalin Alexander, Babadjanova Gulja, Pantelejeva Galina, Abramova Lilia I., Tiganov Alexander S., Polonikov Alexey, Khusnutdinova Elza, Alda Martin, Cruceanu Cristiana, Rouleau Guy A., Turecki Gustavo, Laprise Catherine, Rivas Fabio, Mayoral Fermin, Kogevinas Manolis, Grigoroiu-Serbanescu Maria, Becker Tim, Schulze Thomas G., Rietschel Marcella, Cichon Sven, Fier Heide et Nöthen Markus M.. (2017). Identification of shared risk loci and pathways for bipolar disorder and schizophrenia. PLoS ONE, 12, (2), e0171595.

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URL officielle: http://dx.doi.org/doi:10.1371/journal.pone.0171595

Résumé

Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8 ). This provides further evidence that SCZassociated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.

Type de document:Article publié dans une revue avec comité d'évaluation
Volume:12
Numéro:2
Pages:e0171595
Version évaluée par les pairs:Oui
Date:2017
Sujets:Sciences de la santé > Sciences médicales > Biologie moléculaire
Sciences de la santé > Sciences médicales > Génétique
Département, module, service et unité de recherche:Départements et modules > Département des sciences fondamentales
Mots-clés:Bipolar disorder, schizophrenia, genetic loci, genomic medicine, single nucleotide polymorphisms, genome-wide association studies, GWAS, SNPs
Déposé le:05 avr. 2017 21:59
Dernière modification:05 avr. 2017 21:59
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