Investigating the Contribution of Common Genetic Variants to the Risk and Pathogenesis of ADHD
Abstract
Objective:
Method:
Results:
Conclusions:
Method
Subjects and Clinical Measures
Diagnosis | N | % |
---|---|---|
ADHD diagnoses (lifetime)a | ||
DSM-IV ADHD, combined type | 498 | 64.8 |
DSM-IV ADHD, predominantly inattentive type | 162 | 21.1 |
DSM-IV ADHD, predominantly hyperactive-impulsive type | 62 | 8.1 |
DSM-III-R ADHD | 46 | 6.0 |
Other diagnoses (current) | ||
DSM-IV conduct disorder | 107 | 13.7 |
DSM-IV oppositional defiant disorder | 364 | 46.5 |
DSM-IV anxiety disorder (generalized anxiety disorder, separation anxiety, or social phobia) | 37 | 4.7 |
DSM-IV depressive disorder (any) | 22 | 2.8 |
Genotyping
Quality Control Assessment
CNV Data
Statistical Analysis
GWAS.
Pathway analysis of Cardiff GWAS data.
Overlap of GWAS and CNV pathways.
Results
GWAS
Minor Allele | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
SNP | Chromosome | Position | Closest Gene | Location Relative to Gene | Minor Allele | Other Allele | Minor Allele Frequency | p | Odds Ratio | 95% CI |
rs1744062 | 6 | 137350879 | IL20RA | Within noncoding gene | G | A | 0.43 | 4.16E-06 | 0.75 | 0.67–0.85 |
rs11079828 | 17 | 43964102 | HOXB1 | Upstream | T | C | 0.47 | 6.54E-06 | 1.32 | 1.17–1.49 |
rs42259 | 5 | 14439655 | TRIO | Intronic | T | C | 0.17 | 6.76E-06 | 1.41 | 1.22–1.64 |
rs3779312 | 7 | 77549692 | MAGI2 | Intronic | T | C | 0.21 | 8.38E-06 | 1.37 | 1.19–1.57 |
rs616668 | 12 | 110458663 | ATXN2 | Intronic | G | T | 0.20 | 8.62E-06 | 1.38 | 1.20–1.59 |
rs11175219 | 12 | 62648986 | SRGAP1 | Intronic | T | C | 0.12 | 1.06E-05 | 1.46 | 1.23–1.73 |
rs4238186 | 13 | 18588836 | LOC100128765 | Intergenic | A | G | 0.18 | 1.11E-05 | 1.39 | 1.20–1.61 |
rs7746680 | 6 | 45885325 | - | Intergenic | A | G | 0.24 | 1.14E-05 | 1.35 | 1.18–1.54 |
rs11686538 | 2 | 225526808 | DOCK10 | Intronic | G | A | 0.29 | 1.27E-05 | 0.74 | 0.64–0.84 |
rs1304358 | 2 | 198677828 | PLCL1 | Intronic | C | T | 0.49 | 1.27E-05 | 1.30 | 1.16–1.47 |
rs406742 | 10 | 8885947 | - | Intergenic | G | A | 0.26 | 1.49E-05 | 1.33 | 1.17–1.51 |
rs790531 | 13 | 49623515 | DLEU2 | Within noncoding gene | G | A | 0.06 | 1.50E-05 | 1.62 | 1.30–2.02 |
rs6815704 | 4 | 93693589 | GRID2 | Intronic | A | G | 0.15 | 2.09E-05 | 1.40 | 1.20–1.64 |
rs9842394 | 3 | 181095930 | PEX5L | Intronic | T | C | 0.47 | 2.68E-05 | 0.77 | 0.69–0.87 |
rs2636788 | 10 | 98866931 | SLIT1 | Intronic | G | A | 0.17 | 2.74E-05 | 0.70 | 0.59–0.83 |
rs1490046 | 5 | 173888653 | - | Intergenic | A | G | 0.08 | 2.87E-05 | 1.56 | 1.27–1.92 |
rs1050567 | 2 | 61559167 | XPO1 | 3′ untranslated region | T | C | 0.11 | 2.89E-05 | 1.44 | 1.22–1.72 |
rs9384245 | 6 | 155201820 | TIAM2 | Intronic | T | C | 0.42 | 3.00E-05 | 0.77 | 0.68–0.87 |
rs1370072 | 13 | 54739939 | - | Intergenic | T | C | 0.45 | 3.28E-05 | 1.29 | 1.14–1.45 |
rs874836 | 22 | 15681843 | XKR3 | Intronic | A | G | 0.13 | 3.32E-05 | 1.41 | 1.20–1.67 |
Pathway Analysis of Cardiff SNP Data
Overlap of Enriched Pathways Between CNV and SNP Data
Pathway Numbera | Number of Genes | Gene Hits (Cases) | Gene Hits (Comparison) | p (CNV) | p (corr)b | p (GWAS) | Description |
---|---|---|---|---|---|---|---|
MGI:5278 | 188 | 14 | 0 | 1.47E-05 | 0.002 | 0.030 | Abnormal cholesterol homeostasis |
MGI:3947 | 182 | 13 | 0 | 2.61E-05 | 0.004 | 0.023 | Abnormal cholesterol level |
MGI:180 | 169 | 13 | 0 | 2.61E-05 | 0.004 | 0.026 | Abnormal circulating cholesterol level |
GO:16746 | 214 | 14 | 0 | 1.42E-04 | 0.009 | 0.004 | Transferase activity, transferring acyl groups |
GO:8415 | 203 | 13 | 0 | 1.43E-04 | 0.009 | 0.003 | Acyltransferase activity |
GO:16747 | 205 | 13 | 0 | 1.43E-04 | 0.008 | 0.004 | Transferase activity, transferring acyl groups other than amino-acyl groups |
GO:51298 | 11 | 8 | 0 | 6.95E-04 | 0.050 | 0.033 | Centrosome duplication |
GO:32680 | 34 | 7 | 1 | 8.83E-03 | 0.341 | 0.014 | Regulation of tumor necrosis factor production |
GO:5261 | 271 | 17 | 6 | 1.84E-02 | 0.547 | 0.042 | Cation channel activity |
GO:7417 | 441 | 28 | 10 | 2.77E-02 | 0.683 | 0.002 | Central nervous system development |
GO:16247 | 56 | 8 | 2 | 3.07E-02 | 0.719 | 0.026 | Channel regulator activity |
GO:8233 | 572 | 25 | 8 | 4.89E-02 | 0.848 | 0.037 | Peptidase activity |
GO:70011 | 553 | 25 | 8 | 4.89E-02 | 0.848 | 0.038 | Peptidase activity, acting on L-amino acid peptides |
Discussion
Acknowledgments
Footnotes
Supplementary Material
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