Copy Number Variations in Adult-onset Neuropsychiatric Diseases

• Published in: Current genomics Vol. 19; no. 6; pp. 420 - 430
• Main Authors: Lew, Alexandra R, Kellermayer, Timot R, Sule, Balint P, Szigeti, Kinga
• Format: Journal Article
• Language: English
• Published: United Arab Emirates Bentham Science Publishers Ltd 01.09.2018; Benham Science Publishers; Bentham Science Publishers
• Subjects: Alzheimer's disease; Attention deficit hyperactivity disorder; Bipolar disorder; Copy number; Cortex; Dependence; Diseases; Fusion protein; Gene deletion; Genetic diversity; Genotyping; Heritability; Loci; Medical treatment; Mental disorders; Neurodegenerative diseases; Schizophrenia; Single-nucleotide polymorphism; Adult onset; CNV; Copy number variation; GWAS; Structural variants; Neuropsychiatric diseases
• ISSN: 1389-2029; 1875-5488
• DOI: 10.2174/1389202919666180330153842

Adult-onset neuropsychiatric diseases are one of the most challenging areas of medicine. While symptomatic treatments are available, for most of these diseases the exact pathomechanism is not known, thus, disease-modifying therapies are difficult to conceptualize and find. The two most common and best studied neuropsychiatric diseases affecting higher cortical functions in humans are schizophrenia and Alzheimer’s disease; both diseases have high heritability, however, the genetic architecture is not fully elucidated. Robust Single Nucleotide Variant (SNV) studies have identified several loci with modest effect sizes. While Copy Number Variants (CNV) make an important contribution to genetic variation, CNV GWAS suffer from dependence on mainly SNP arrays with underperforming genotyping accuracy. We evaluated dynamic range of the assays for three types of CNV loci, including biallelic deletion, high copy gain, and fusion gene, to assess the depth of exploration of the contribution of CNVs to disease susceptibility. Despite the suboptimal genotyping, novel mechanisms are emerging and further large-scale studies with genotyping assays optimized for CNV detection are needed. Furthermore, the CHRFAM7A human-specific fusion gene association warrants large scale locus specific association studies in AD, schizophrenia, bipolar disorder and ADHD.