Introduction
Methods
Study subjects
Clinical measures
Selection of single nucleotide polymorphisms
Genotyping
Quality control
Family-based association analysis
Results
Sample description
SNP ID | MAF | Gene name | CHR | Gene function | Type of reference study | Sample size reference study |
χ
2 statistic reference study | OR reference study | No. of parent–child trios after quality control in present study | Power in present studya
| References |
---|---|---|---|---|---|---|---|---|---|---|---|
Implicated in TS | |||||||||||
rs1800497 | 0.18 |
ANKK1/DRD2
| 11 | Serine/threonine kinase | Case–control | 147 TS/314 controls | 19.4 | 179 | [3] | ||
rs9357271b
| 0.24 |
BTBD9
| 6 | Protein–protein interactions | Case–control | 322 TS/290 controls | 8.02 | 371 | [32] | ||
rs11264126c | 0.49 |
DLGAP3
| 1 | Post-synaptic scaffolding protein | TDT | 289 parent–child trios | 1.41 | 371 | 0.91 | [33] | |
rs12141243 | 0.11 |
DLGAP3
| 1 | Post-synaptic scaffolding protein | TDT | 289 parent–child trios | 1.04 | 179 | <0.10 | [33] | |
rs6279 | 0.31 |
DRD2
| 11 | Dopamine receptor | TDT | 69 parent–child trios | 11.5 | 179 | [34] | ||
rs1079597 | 0.11 |
DRD2
| 11 | Dopamine receptor | TDT | 69 parent–child trios | 11.5 | 371 | [34] | ||
rs4648318 | 0.25 |
DRD2
| 11 | Dopamine receptor | TDT | 69 parent–child trios | 11.5 | 371 | [34] | ||
rs854150 | 0.36 |
HDC
| 15 | Histamine synthesis | TDT | 520 TS families | 8.13 | 179 | [35] | ||
rs518147 | 0.37 |
HTR2C
| X | Serotonin receptor | Case–control | 87 TS/311 controls | 2.50 | 179 | 0.99 | [36] | |
rs3813929 | 0.18 |
HTR2C
| X | Serotonin receptor | Case–control | 87 TS/311 controls | 1.89 | 371 | 0.99 | [36] | |
rs6347 | 0.24 |
SLC6A3/DAT1
| 5 | Dopamine transporter | Case–control | 266 cases/236 controls | 8.40 | 1.78d
| 179 | 0.92 | [37] |
rs9593835e
| 0.26 |
SLITRK1
| 13 | Neurite outgrowth | TDT | 154 TS families | 6.22 | 1.66f
| 371 | 0.99 | [38] |
rs9531520 | 0.19 |
SLITRK1
| 13 | Neurite outgrowth | TDT | 154 TS families | 6.22 | 1.45f
| 179 | 0.55 | [38] |
rs3744161 | 0.46 |
TBCD
| 17 | Tubulin folding protein | TDT | 100 TS families | 179 | [39] | |||
rs662669 | 0.42 |
TBCD
| 17 | Tubulin folding protein | TDT | 100 TS families | 179 | [39] | |||
rs4565946 | 0.49 |
TPH2
| 12 | Serotonin synthesis | Case–control | 98 TS/178 controls | 1.95/1.65g
| 371 | 0.99/0.99g
| [31] | |
rs4570625 | 0.2 |
TPH2
| 12 | Serotonin synthesis | Case–control | 98 TS/178 controls | 1.95/1.65g
| 371 | 0.99/0.98g
| [31] | |
Implicated in related disorders | |||||||||||
rs4680 | 0.47 |
COMT
| 22 | Dopamine degradation | Meta-analysis | 47,358 cases OCD/68,942 controls/2433 OCD parent–child trios | 371 | [40] | |||
rs7794745 | 0.31 |
CNTNAP2
| 7 | Cell adhesion molecule | TDT | 145 autism parent–child trios and 78 sib-pairs | 371 | [41] |
Gene | # of tSNPs | # of tSNPs excluded following QCa
| CHR | Neurotransmitter pathway | Function | Sample size reference study | References |
---|---|---|---|---|---|---|---|
TS neurotransmitter-related candidate genes | |||||||
DRD2
| 14 | 11 | Dopamine | Dopamine receptor | 147 TS/314 controls | [3] | |
HDC
|
11
| 15 | Histamine | Histamine synthesis | 520 TS families | [17] | |
MAO-A
|
9
| 1 | X | Serotonin (5-HT), dopamine | Degradation of dopamine and 5-HT | 110 TS parent–child trios | [4] |
SLC6A3/DAT1
|
21
| 3 | 5 | Dopamine | Dopamine transporter | 266 cases/236 controls | [37] |
TPH2
|
19
| 12 | Serotonin (5-HT) | 5-HT synthesis | 149 TS/125 controls | [42] | |
Candidate genes implicated in related disorders | |||||||
GABRA2
| 14 | 4 | GABA | GABA receptor | 470 autism families | [14] | |
SLC1A1
| 52 | 9 | Glutamate | Glutamate transporter | 377 OCD families | [15] | |
Newly investigated candidate gene | |||||||
HRH3
| 8 | 2 | 20 | Histamine | Histamine receptor |
SNP
| MAF | Gene name | CHR | Function | Sample size reference study | No. of parent–child trios after quality control in present study | References |
---|---|---|---|---|---|---|---|
TS GWAS SNPs | |||||||
rs7868992 | 0.28 |
COL27A1
| 9 | Calcification of cartilage and the transition of cartilage to bone | 1285 cases/4964 controls | 371 | [6] |
rs621942 | 0.24 |
PICALM
| 11 | Endocytosis | 1894 cases/5574 controls | 192 | [7] |
rs6539267 | 0.27 |
POLR3B
| 12 | DNA-dependent RNA polymerase | 1285 cases/4964 controls | 371 | [6] |
rs4988462 | 0.44 |
POU1F1
| 3 | Transcription factor | 2723 cases/5667 controls | 179 | [20] |
rs7123010 | 0.27 |
ME3
| 11 | Malate metabolism | 1894 cases/5574 controls | [7] | |
rs2060546a
| 0.01 | 12 | 1894 cases/5574 controls | [7] | |||
rs13063502 | 0.18 | 3 | 1285 cases/4964 controls | 371 | [6] | ||
rs769111 | 0.37 | 7 | 1285 cases/4964 controls | 179 | [6] | ||
rs7336083 | 0.33 | 13 | 1285 cases/4964 controls | 371 | [6] | ||
rs11603305 | 0.32 | 11 | 1894 cases/5574 controls | 192 | [7] | ||
rs11149058 | 0.22 | 13 | 2723 cases/5667 controls | 179 | [20] | ||
rs4271390a
| 0.22 | 11 | 2723 cases/5667 controls | [20] | |||
OCD GWAS SNPs | |||||||
rs11081062 | 0.19 |
DLGAP1
| 18 | Scaffold protein | 1465 cases/5557 controls/400 parent–child trios | 371 | [21] |
rs9499708 | 0.42 | 6 | 1465 cases/5557 controls/400 parent–child trios | 179 | [21] | ||
rs9652236 | 0.15 | 13 | 1465 cases/5557 controls/400 parent–child trios | 371 | [21] | ||
rs6131295 | 0.23 | 20 | 1465 cases/5557 controls/400 parent–child trios | 371 | [21] | ||
rs297941a
| 0.44 | 12 | 1465 cases/5557 controls/400 parent–child trios | [21] | |||
ADHD GWAS SNPs | |||||||
rs2556378 | 0.18 |
BCL11A
| 2 | Myeloid and B-cell proto-oncogene | 495 cases/1300 controls | 179 | [22] |
rs12575642 | 0.15 |
FERMT3
| 11 | Cell adhesion | 465 trios | 371 | [23] |
rs5016282 | 0.15 |
GRM5
| 11 | Glutamate receptor | 495 cases/1300 controls | 179 | [22] |
rs12037173 | 0.07 |
LRRC7
| 1 | Cell adhesion, dendritic branching, and neuronal excitability | 465 parent–child trios | 179 | [23] |
rs11607165 | 0.15 |
STIP1
| 11 | Response to stress | 465 parent–child trios | 371 | [23] |
ASD GWAS SNPs | |||||||
rs1718101 | 0.07 |
CNTNAP2
| 7 | Cell adhesion | 2705 families | 179 | [24] |
rs4675502 | 0.37 |
PARD3B
| 2 | Cell division and cell polarization | 2705 families | 179 | [24] |
rs4150167a
| 0.04 |
TAF1C
| 16 | Transcription factor | 2705 families | [24] | |
rs4307059 | 0.37 | 5 | 780 families/1204 cases/6491 cases | 179 | [25] | ||
rs13176113b
| 0.28 | 5 | 780 families/1204 cases/6491 cases | 179 | [25] | ||
rs7834018 | 0.10 | 8 | 2705 families | 371 | [24] | ||
rs7711337 | 0.40 | 5 | 2705 families | 371 | [24] |
Transmission disequilibrium tests
Candidate SNPs previously implicated in TS
SNP | CHR | BP | Gene | Minor/major allele | MAF | Over-transmitted allele | T:U | ORa
| 95% CIa
|
χ
2 b
|
P value nominalc
|
P value adjusted (FDR)d
| OR TS GWASe
|
P value TS GWASe
|
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Nominally significant candidate SNPs previously implicated in TS | ||||||||||||||
rs3744161 | 17 | 80828057 |
TBCD
| G/C | 0.49 | Minor | 123:91 | 1.35 | 1.03–1.77 | 5.45 | 0.03 | 0.64 | 0.97 | 0.31 |
rs4565946 | 12 | 72336769 |
TPH2
| T/C | 0.49 | Minor | 205:163 | 1.26 | 1.02–1.55 | 6.01 | 0.02 | 0.57 | 1.01 | 0.81 |
Nominally significant tSNPs from candidate genes previously implicated in TS or OCD | ||||||||||||||
rs17812372 | 9 | 4519989 |
SLC1A1
| G/C | 0.04 | Minor | 49:24 | 2.04 | 1.25–3.33 | 11.23 | 0.0006 | 0.11 | 1.06 | 0.29 |
rs1042098f
| 5 | 1394815 |
SLC6A3/DAT1
| G/A | 0.29 | Minor | 159:118 | 1.35 | 1.06–1.71 | 4.96 | 0.03 | 0.71 | 1.00 | 0.98 |
rs11615016f
| 12 | 72415994 |
TPH2
| G/A | 0.03 | Minor | 42:28 | 1.5 | 0.93–2.42 | 7.35 | 0.006 | 0.57 | 0.97 | 0.63 |
rs4760813f
| 12 | 72322894 |
TPH2
| C/G | 0.30 | Major | 58:39 | 1.49 | 0.99–2.23 | 4.24 | 0.04 | 0.71 | 1.01 | 0.85 |
rs7969998f
| 12 | 72328745 |
TPH2
| C/T | 0.05 | Major | 57:41 | 1.39 | 0.93–2.08 | 7.38 | 0.01 | 0.57 | 0.95 | 0.29 |
Nominally significant SNPs from TS GWAS studies | ||||||||||||||
rs11603305 | 11 | 10997949 | Intergenic | G/A | 0.32 | Minor | 125:92 | 1.36 | 1.04–1.78 | 6.11 | 0.02 | 0.24 | ||
rs621942 | 11 | 85783738 |
PICALM
| A/C | 0.24 | Minor | 121:84 | 1.44 | 1.09–1.90 | 7.08 | 0.01 | 0.24 |