Title:Copy Number Variations in Adult-onset Neuropsychiatric Diseases
VOLUME: 19 ISSUE: 6
Author(s):Alexandra R. Lew, Timot R. Kellermayer, Balint P. Sule and Kinga Szigeti*
Affiliation:Department of Neurology, University at Buffalo, SUNY, Buffalo, NY 14203, Department of Neurology, University at Buffalo, SUNY, Buffalo, NY 14203, Department of Neurology, University at Buffalo, SUNY, Buffalo, NY 14203, Department of Neurology, University at Buffalo, SUNY, Buffalo, NY 14203
Keywords:Copy number variation, CNV, GWAS, Neuropsychiatric diseases, Adult onset, Structural variants.
Abstract: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.
