Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies
Abstract
Objective:
Methods:
Results:
Conclusions:
Methods
Study Subjects
GWAS1.
GWAS2.
GWAS2 FAM.
TIC.
Control subjects.
deCODE.
Quality Control
Imputation and Genome-Wide Association
Heritability Estimation
Targeted Replication
Polygenic Risk Score Analyses
Gene-Based and Gene Set Enrichment Analysis
Results
Genome-Wide Association Study
Primary Meta-Analysis | deCODE Sample | Primary and deCODE Sample | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SNP | CHR | BP | A1/A2 | INFO Score | MAF | Odds Ratio | p | MAF | Odds Ratio | p | Odds Ratio | p | LD Block | Genes |
rs2504235 | 13 | 28,612,886 | A/G | 0.99 | 0.38 | 1.16 | 2.1E–08 | 0.32 | 0.94 | 0.50 | 1.14 | 2.4E–07 | 28591318.28659473 | FLT3 |
rs191044310 | 10 | 23,705,451 | A/T | 0.83 | 0.02 | 0.54 | 1.5E–07 | 0.0024 | 2.27 | 0.25 | 0.56 | 5.9E–07 | 23661149.23815120 | OTUD1 |
rs13407215 | 2 | 161,544,891 | T/C | 1.00 | 0.02 | 2.21 | 1.9E–07 | 0.0001 | 0.02 | 0.85 | 2.21 | 1.9E–07 | 160090844.162912453 | Multiple genesc |
rs2708146 | 2 | 58955953 | G/A | 1.009 | 0.46 | 0.88 | 3.2E–07 | 0.48 | 0.98 | 0.75 | 0.89 | 8.0E–07 | 58847953.59094609 | LINC01122 |
rs1906252b | 6 | 98,550,289 | A/C | 1.00 | 0.49 | 0.88 | 7.0E–07 | 0.50 | 0.90 | 0.17 | 0.88 | 2.8E–07 | 98214814.98664414 | MIR2113 |
rs12459560 | 19 | 52,318,380 | T/G | 0.98 | 0.15 | 1.19 | 8.2E–07 | 0.16 | 1.08 | 0.45 | 1.18 | 9.1E–07 | 52266072.52606936 | Multiple genesd |
rs117648881 | 8 | 113,581,898 | A/G | 0.77 | 0.02 | 0.59 | 8.8E–07 | 0.01 | 0.72 | 0.32 | 0.60 | 6.2E–07 | 113581898.114612903 | CSMD3, MIR2053 |
rs6670211 | 1 | 29,576,784 | A/C | 1.00 | 0.47 | 0.88 | 1.4E–06 | 0.42 | 0.94 | 0.45 | 0.89 | 1.5E–06 | 29188630.29607279 | EPB41, MECR, OPRD1, PTPRU, SRSF4, TMEM200B |
rs72853320 | 6 | 36,623,338 | A/G | 1.00 | 0.13 | 1.20 | 1.7E–06 | 0.12 | 0.88 | 0.28 | 1.17 | 2.2E–05 | 36375986.36658092 | CDKN1A, KCTD20, MIR3925, PANDAR, PXT1, RAB44, SRSF3, STK38 |
rs73205493 | 4 | 2,460,571 | T/C | 0.89 | 0.34 | 1.16 | 1.8E–06 | 0.35 | 1.08 | 0.34 | 1.15 | 1.6E–06 | 2407263.2481088 | LOC402160, RNF4, ZFYVE28 |
Targeted Replication
Heritability and PRS Analyses
Case Subjects | Control Subjects | ||||||
---|---|---|---|---|---|---|---|
Sample | N | % | N | % | V(G)/Vp_Lb | SE | p |
GWAS1 | 559 | 14 | 3,400 | 86 | 0.565 | 0.096 | 1.2×10–9 |
GWAS2c | 2,146 | 46 | 2,564 | 54 | 0.288 | 0.040 | 5.5×10–14 |
GWAS2c web-based | 934 | 27 | 2,564 | 73 | 0.294 | 0.067 | 2.4×10–6 |
GWAS2c clinic-based | 1,098 | 30 | 2,564 | 70 | 0.284 | 0.059 | 4.0×10–7 |
Tourette’s Syndrome PRS in Multiplex Versus Simplex Families
Tourette’s Syndrome PRS and Tic Severity
Tourette’s Syndrome and Tic Spectrum Phenotypes
Enrichment of Tourette’s Syndrome Heritability by Functional Annotation and Gene Expression
Gene-Based Association and Enrichment Analyses
Discussion
Limitations
Acknowledgments
Footnotes
Supplementary Material
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