Table 4.
Significant Combined and Adaptive Sum Test Results of Cumulative Rare- and Common-Variant Effects on Smoking Status in AA and EA Samples
| Gene | AA Sample | EA Sample | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Rare variant(s) | Common variant(s) | Effect direction | P value† Separated | Pooled | Rare variant(s) | Common variant(s) | Effect direction | P-value† | ||
| Separated | Pooled | |||||||||
| NRXN1 |
rs77665267 (p.T274P) -(p.S62*) |
rs10208208 rs6721498 |
↑ | 0.5553 0.3023 0.5354 0.2996 |
0.5537 0.9368 0.5398 0.9275 |
rs77665267 (p.T274P) rs10208208 |
rs10490227 | ↑ | 0.1016 0.0527 0.0738 0.0362 |
0.1062 0.0772 0.0683 0.0505 |
|
- (p.R206L) - (p.Y367*) |
rs10490227 rs2193225 |
↓ | 0.4244 0.1991 0.5232 0.3547 |
- (p.R206L) |
rs6721498 rs2193225 |
↓ | 0.4648 0.2849 0.4506 0.4596 |
|||
| CHRNA9 |
rs139982841 (p.A452V) |
↑ | 0.2381 0.2381 0.2381 0.2381 |
0.0706 0.0766 0.1448 0.0495 |
rs142807401 (p.A432T) |
rs55633891 (p.A315V) |
↑ |
0.0143 0.0143 0.0246 0.0246 |
0.0012 0.0032 0.0036 0.0080 |
|
|
rs142807401 (p.A432T) |
rs56210055 (p.A312T) rs55633891 (p.A315V) |
↓ |
0.0381 0.0143 0.0942 0.0353 |
rs56210055 (p.A312T) rs139982841 (p.A452V) |
↓ |
0.0119 0.0072 0.0119 0.0072 |
||||
| DRD1 | - (p.R226W) |
rs265975 rs4532 |
↑ | 0.0572 0.0393 0.0549 0.0372 |
0.1121 0.0458 0.1224 0.0430 |
N/A | ||||
| rs686 | ↓ | 0.8101 0.8101 0.8101 0.8101 |
||||||||
| ANKK1/DRD2 |
rs56299709 (p.E376K) - (p.R734C) - (p.E181*) rs2075654 |
rs111789052 (p.C52W) rs115800217 (p.R185Q) rs11604671 (p.G328R) rs78229381 (p.R445C) rs2734849 (p.H490R) |
↑ | 0.4445 0.1179 0.3915 0.1370 |
0.3915 0.0950 0.4850 0.1361 |
rs111789052 (p.C52W) rs35877321 (p.R122H) rs56299709 (p.E376K) rs78229381 (p.R445C) rs184645039 (p.E458G) - (p.R734C) |
rs2075654 rs4586205 |
↑ | 0.3828 0.1708 0.2649 0.1303 |
0.5566 0.8627 0.4306 0.8619 |
|
rs35877321 (p.R122H) rs56047699 (p.R237*) - (p.S313*) rs186633697 (p.P351S) rs184645039 (p.E458G) rs113005509 (p.E587*) rs202222056 (p.Q657*) rs2075652 |
rs4586205 | ↓ | 0.4965 0.0371 0.5029 0.0273 |
rs115800217 (p.R185Q) rs56047699 (p.R237*) - (p.S313*) rs113005509 (p.E587*) - (p.E181*) rs2075652 |
rs11604671 (p.G328R) rs2734849 (p.H490R) |
↓ | 0.7714 0.3605 0.8413 0.2840 |
|||
| CHRNA5/ A3/B4 |
rs72650603 (p.H217Y) rs8192475 (p.R37H) - (p.R497C) - (p.F462V) rs56235003 (p.R349C) - (p.P145A) rs12914008 (p.T91I) rs75495090 (p.N41S) |
rs16969968 (p.D398N) rs1051730 (p.Y215Y) |
↑ | 0.0901 0.0323 0.0701 0.0596 |
0.2406 0.4546 0.1398 0.4909 |
rs2229961 (p.V134I) rs72650603 (p.H217Y) rs8192475 (p.R37H) |
rs588765 rs16969968 (p.D398N) rs1051730 (p.Y215Y) |
↑ | 0.7389 0.2600 0.6989 0.3322 |
0.7570 0.9566 0.7185 0.9078 |
|
rs2229961 (p.V134I) rs80087508 (p.K167R) rs56218866 (p.S140G) |
rs588765 rs578776 rs6495308 |
↓ | 0.5737 0.4017 0.4497 0.4983 |
rs80087508 (p.K167R) rs56235003 (p.R349C) rs56218866 (p.S140G) rs12914008 (p.T91I) rs75495090 (p.N41S) |
rs578776 rs6495308 |
↓ | 0.6270 0.3729 0.5879 0.5716 |
|||
Notes:
1) P values for each gene or region were obtained by four statistical methods; i.e., SKAT-C, Burden-C, SKAT-A, and Burden-A;
= p values from top to bottom for each gene or region were obtained in the abovementioned order.
2) Only genes or regions with at least one rare and one common variant were eligible for the pooled analysis; N/A = not applicable.
3) “↑” = variants increase smoking risk estimated from individual variant-based odds ratios (if available) or minor allele counts in Cases and Controls, “↓” = variants decrease smoking risk; effect direction specific tests were applied with p values listed under “Separated”.
4) SNP rs numbers are based on dbSNP database (accessed on 2/17/2014).
5) SNPs included in both AA and EA samples for this analysis are underlined.
6) Nominal significant associations (p< 0.05) for both “Pooled” and “Separated” analyses are given in bold, including p values, SNP, and gene names. See the section of “Materials and Methods” for details.