Author:

Keywords:

Bipolar Disorder, Calcineurin, Cyclic AMP Response Element Modulator, Cyclic AMP Response Element-Binding Protein, Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Male, Middle Aged, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Schizophrenia, Sweden, Science & Technology, Life Sciences & Biomedicine, Psychiatry, Genomics, Synaptic genes, Psychiatric genetics, Neural plasticity, CONVERGENT FUNCTIONAL GENOMICS, SCAN METAANALYSIS, CANDIDATE GENES, MICE, IDENTIFICATION, DYSFUNCTION, PATHWAYS, GENETICS, STRESS, White People, 11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences, 3202 Clinical sciences

Abstract:

Identification of novel candidate genes for schizophrenia (SZ) and bipolar disorder (BP), two psychiatric disorders with large epidemiological impacts, is a key research area in neurosciences and psychiatric genetics. Previous evidence from genome-wide studies suggests an important role for genes involved in synaptic plasticity in the risk for SZ and BP. We used a convergent genomics approach, combining different lines of biological evidence, to identify genes involved in the cAMP/PKA/CREB functional pathway that could be novel candidates for BP and SZ: CREB1, CREM, GRIN2C, NPY2R, NF1, PPP3CB and PRKAR1A. These 7 genes were analyzed in a HapMap based association study comprising 48 common SNPs in 486 SZ, 351 BP patients and 514 control individuals recruited from an isolated population in Northern Sweden. Genetic analysis showed significant allelic associations of SNPs in PRKAR1A with SZ and of PPP3CB and PRKAR1A with BP. Our results highlight the feasibility and the importance of convergent genomic data analysis for the identification of candidate genes and our data provide support for the role of common inherited variants in synaptic genes and their involvement in the etiology of BP and SZ.