Autism Spectrum Disorder study with SNP Genotypes (Array) data on dbGaP (4,384 participants)

phs001881 — A Large Data Resource of Genomic Copy Number Variation across    Neurodevelopmental Disorders

This study presents the first genome-wide copy number variation (CNV) analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD). A total of 2,691 subjects diagnosed with a neurodevelopmental disorder (NDD), and a total of 1,769 unaffected family members from Ontario, Canada were assayed using the Affymetrix CytoScan HD array. We identified rare CNVs, (&#x3C; 0.1% frequency in 10,851 population control samples), and found clinically relevant CNVs in 10.5% of total subjects. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence) are <a href="https://www.ncbi.nlm.nih.gov/gene/9378">NRXN1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/81929">SEH1L</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/753">LDLRAD4</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/2774">GNAL</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/51764">GNG13</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/23608">MKRN1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/10540">DCTN2</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/85442">KNDC1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/55251">PCMTD2</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/3798">KIF5A</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/23336">SYNM</a>, and long non-coding RNAs: <a href="https://www.ncbi.nlm.nih.gov/gene/?term=AK127244">AK127244</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/641373">NRON</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/?term=PTCHD1-AS">PTCHD1-AS</a>. We demonstrated that identical CNVs or genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants and clinical interpretations.CNV data from this study are available through dbVar at <a href="https://www.ncbi.nlm.nih.gov/dbvar/studies/nstd173/">https://www.ncbi.nlm.nih.gov/dbvar/studies/nstd173/</a>.