Prevalence and Penetrance of Rare Pathogenic Variants in Neurodevelopmental Psychiatric Genes in a Health Care System Population
Abstract
Objective:
Methods:
Results:
Conclusions:
Methods
Participants
Exome Sequencing and Variant Calling
Evidence-Based Approach to NPD Gene Selection
LOF Variant Frequency in NPD Genes From the DiscovEHR and gnomAD Non-Finnish European (NFE) Populations
NPD Diagnosis Extraction
Analysis of Prevalence and Penetrance of Pathogenic Variants
Statistical Analysis
Results
Prevalence of NPD-Related Single-Gene Variants
Estimated Penetrance of NPD Gene Variants
Associations Between Rare Genomic Variants and NPD Diagnosis
Disorder | Odds Ratio | 95% CI | Corrected p | Uncorrected p | Cases With a Variant (N) | Total Cases (N) | Controls With a Variant (N) | Total Controls (N) |
---|---|---|---|---|---|---|---|---|
Intellectual disability | 8.73 | 4.83, 14.72 | 1.91×10–8 | 1.36×10–9 | 15 | 423 | 260 | 81,304 |
ASD | 4.56 | 1.58, 11.35 | 0.10 | 6.85×10–3 | 6 | 229 | 269 | 81,498 |
ADHD | 2.89 | 1.83, 4.40 | 2.57×10–4 | 1.84×10–5 | 27 | 2,397 | 248 | 79,330 |
Epilepsy | 2.39 | 1.56, 3.51 | 2.11×10–3 | 1.51×10–4 | 26 | 3,311 | 249 | 78,416 |
Schizophrenia and related disorders | 2.88 | 1.75, 4.45 | 1.47×10–3 | 1.05×10–4 | 19 | 2,234 | 256 | 79,493 |
Bipolar disorder | 2.32 | 1.54, 3.39 | 2.04×10–3 | 1.45×10–4 | 29 | 3,636 | 246 | 78,091 |
Communication disorder | 3.47 | 1.86, 5.97 | 3.92×10–3 | 2.80×10–4 | 13 | 901 | 262 | 80,826 |
Specific learning disorder | 5.52 | 2.74, 10.11 | 2.46×10–4 | 1.76×10–5 | 11 | 447 | 264 | 81,280 |
Cerebral palsy | 2.06 | 0.23, 7.53 | >0.99 | 0.433 | 1 | 161 | 274 | 81,566 |
OCD | 1.47 | 0.55, 3.11 | >0.99 | 0.406 | 5 | 966 | 270 | 80,761 |
Other neurodevelopmental disorder | 5.89 | 2.68, 11.86 | 6.41×10–4 | 4.58×10–5 | 11 | 406 | 264 | 81,321 |
Motor disorder | 2.00 | 0.93, 3.73 | >0.99 | 0.074 | 8 | 1,196 | 267 | 80,531 |
Anxiety | 1.14 | 0.89, 1.46 | >0.99 | 0.286 | 126 | 34,611 | 149 | 47,116 |
Depressive disorder | 1.47 | 1.15, 1.87 | 2.58×10–2 | 1.84×10–3 | 133 | 32,057 | 142 | 49,670 |
Sensitivity Analyses
Discussion
Conclusions
Acknowledgments
Supplementary Material
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