Background
Methods
Study samples
Genotyping and quality control procedures
Association analysis
Results
Cluster headache patients | Controls | |
---|---|---|
N
| 99 | 359 |
Gender (N,%) | ||
Male | 83, 83.84% | 204, 56.82% |
Female | 16, 16.16% | 155, 43.18% |
Age, ys (mean ± sd, range) | 47.39 ± 13.12, 23–81 | 48.96 ± 11.91, 18–70 |
CH attacks | ||
Age at onset, ys (mean ± sd, range) | 30.04 ± 12.65, 6–80 | |
Chronic (N, %) | 14, 14.14% | |
N attacks/year (mean ± sd, range) | 1.29 ± 0.77, 0.17–4 | |
N attacks/day (mean ± sd, range) | 2.85 ± 1.68, 1–9 | |
Smoking | ||
Ever smoking (N,%) | 88, 88.89% | 359, 100% |
N cigarette/day (mean ± sd) | 19.17 ± 10.83 | 21.77 ± 9.13 |
Fagerström test (mean ± sd); N
| 4.60 ± 2.54 (N = 72) | 5.95 ± 2.21 |
Genome wide association analysis
Index SNP | Position | Other SNPs in clump | Gene | A 1 | A 2 | A1-F case/controls | A1-F 1000G_all (1000G_EUR)a
|
P-value | OR (95% CI) |
---|---|---|---|---|---|---|---|---|---|
rs1006417 | 14:41803291 | rs1782180, rs1779522, rs1778408, rs11157219, rs715334, rs12433558 | G | A | 0.11/0.26 | 0.19 (0.19) | 1.40 × 10−6
| 0.34 (0.21–0.55) | |
rs12668955 | 7:31116168 | ADCYAP1R1 | G | A | 0.34/0.52 | 0.55 (0.50) | 9.10 × 10−6
| 0.48 (0.34–0.66) | |
rs1495452 | 3:65834076 | MAGI1 | A | G | 0.55/0.38 | 0.39 (0.45) | 1.43 × 10−5
| 2.03 (1.48–2.79) | |
rs2182605 | 1:117463537 | PTGFRN | G | A | 0.32/0.50 | 0.51 (0.48) | 1.80 × 10−5
| 0.49 (0.35–0.68) | |
rs16895584 | 8:122518935 | A | G | 0.24/0.04 | 0.070 (0.054) | 1.85 × 10−5
| 3.50 (2.03–6.02) | ||
rs6469999 | 8:122415207 | rs13255877, rs7833779 | A | G | 0.31/0.17 | 0.46 (0.16) | 2.16 × 10−5
| 2.23 (1.56–3.19) | |
rs1509957 | 10:64610718 | rs224308, rs10822065 | G | A | 0.60/0.43 | 0.43 (0.49) | 2.66 × 10−5
| 1.99 (1.44–2.74) |
Gene based analysis
SNP | SKAT
P-value | Single SNPs P-valuea
| RA | RAF case/control | RAF 1000G_all (1000G_EUR)b
| RAF in ExAC_all (ExAC_NFE)c
| Function | PolyPhen-2 (Prediction)d
| CADD scoree
|
---|---|---|---|---|---|---|---|---|---|
Gene MME
(NM_000902.3) |
2.55 × 10
−5
| ||||||||
rs61762319 | 0.42 | G | 0.030/0.021 | 0.0072(0.023) | 0.0164(0.0226) | Missense c.22A > G (p.M8V) | 0.524(P) | 15.63 | |
rs147564881 | 2.03 × 10−5
| C | 0.035/0 | 0.001(0.002) | 0.0022(0.0033) | Missense c.674G > C (p.G225A) | 1 (D) | 21 | |
rs61758194 | 1 | A | 0/0.0014 | 0.0002(0) | 0.0021(0.0035) | Missense c.1033G > A (p.V345I) | 0.001(B) | 11.65 | |
Gene NPY1R
(NM_000909.5) |
1.18 × 10
−3
| ||||||||
rs5578 | 3.80 × 10−3
| C | 0.040/0.0084 | 0.003(0.007) | 0.0047(0.0067) | Missense c.1121A > C (p.K374T) | 0.421(B) | 12.96 | |
rs78156188 | 1 | A | 0/0.0028 | 0.0004(0.002) | 0.0006(0.001) | Missense c.332C > T (p.A111V) | 0.023(B) | 3.073 | |
Gene BDKRB1
(NM_000710.3) |
3.30 × 10
−3
| ||||||||
rs143823168 | 1 | C | 0/0.0028 | 0.0018(0.003) | 0.0024(0.0036) | Missense c.571C > G (p.L191V) | 0.999(D) | 9.214 | |
rs45528332 | 9.23 × 10−3
| A | 0.030/0.0056 | 0.0036(0.004) | 0.0062(0.0052) | Missense c.721G > A (p.G241R) | 0.926(P) | 9.661 | |
Gene SLC5A3
(NM_006933.6) |
4.94 × 10
−3
| ||||||||
rs35707420 | 0.014 | A | 0.025/0.0042 | 0.0026(0.006) | 0.0062(0.0087) | Missense c.1108G > A(p.V370M) | 1(D) | 18.46 | |
rs199948762 | 0.39 | G | 0.0051/0.0014 | . | 0.000099 (0.0001) | Missense c.1671C > G(p.N557K) | 0.001(B) | 8.533 | |
Gene CCL26
(NM_006072.4) |
7.02 × 10
−3
| ||||||||
rs41463245 | 0.022 | A | 0.020/0.0028 | 0.0036(0.016) | 0.0086(0.0131) | Nonsense c.132G > A (p.W44X) | . | 23.1 | |
Gene GRM1
(NM_000838.3) |
9.45 × 10
−3
| ||||||||
rs41305288 | 0.017 | A | 0.035/0.0098 | 0.01(0.017) | 0.0172(0.0185) | Missense c.2185C > A (p.P729T) | 1(D) | 19.24 | |
rs362936 | 1 | A | 0.0051/0.0097 | 0.004(0.017) | 0.0212(0.031) | Missense c.2651G > A (p.G884E) | 0.998(D) | 13.22 | |
rs138759146 | 1 | C | 0/0.0014 | . | 0.0001(0.0002) | Missense c.2725A > C (p.M909L) | 0.017(B) | 1.328 | |
rs2941 | 0.14 | A | 0.0051/0.022 | 0.0092(0.025) | 0.0132(0.0182) | Missense c.2785G > A (p.V929I) | 0.111(B) | 18.3 | |
rs79336287 | 0.071 | A | 0.015/0.0023 | 0.005(0.004) | 0.0017(0.0013) | Missense c.3206C > T (p.P1069L) | 0(B) | 11.39 |