Table 2.
SNPs with evidence for independent association at 10 loci with P < 5×10−8. A SNP at the LIG3 locus met our significance threshold in an interim analysis and was confirmed in the QTSCD consortium study. Chromosomal positions and coded alleles are given relative to forward strand of NCBI build 36. Effect sizes are shown as beta estimates from linear regression models for increasing copy of the coded allele and are on the standard deviation scale (1 SD ≈ 17.5 msec). A beta estimate of 0.08 SD is equivalent to a change in QT interval of 1.4 msec and an effect of 0.48 SD is equivalent to an 8.4 msec change. The effective sample size reflects the power relative to the total sample size of 13,685 with imputed data resulting from variation in imputation quality (see Methods). Selected genes from each locus are shown for reference. Results using the same coded allele from the QTSCD study (reported separately) and meta-analysis of the QTGEN and QTSCD study using inverse variance weighting are shown (n ≤ 29,539). Chr = chromosome. SE = standard error.
| QTGEN | QTSCD | Meta-analysis QTGEN + QTSCD |
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| SNP | Chr | Function/gene | Other genes within 500kb at novel loci |
Coded allele |
Allele frequency |
Effective sample size |
Beta estimate |
SE | P-value | Beta estimate |
SE | P-value | Beta estimate |
SE | P-value |
| rs12143842 | 1q | upstream NOS1AP | T | 0.26 | 13,241 | 0.21 | 0.02 | 8×10−46 | 0.16 | 0.01 | 5×10−36 | 0.18 | 0.01 | 2×10−78 | |
| rs12029454 | 1 | intron NOS1AP | A | 0.15 | 12,172 | 0.21 | 0.02 | 6×10−28 | 0.15 | 0.02 | 3×10−20 | 0.17 | 0.01 | 3×10−45 | |
| rs16857031 | 1 | intron NOS1AP | G | 0.14 | 13,154 | 0.19 | 0.02 | 3×10−23 | 0.12 | 0.02 | 1×10−14 | 0.15 | 0.01 | 1×10−34 | |
| rs2074238 | 11p | intron KCNQ1 | T | 0.06 | 2,888 | −0.47 | 0.06 | 3×10−16 | −0.33 | 0.14 | 0.02 | −0.45 | 0.05 | 3×10−17 | |
| rs37062 | 16q | intron CNOT1 | GINS3, NDRG4, SLC38A7, GOT2 | G | 0.24 | 13,440 | −0.12 | 0.02 | 3×10−15 | −0.09 | 0.01 | 5×10−12 | −0.10 | 0.01 | 3×10−25 |
| rs11756438 | 6q | intron c6orf204 | SLC35F1, PLN, ASF1A | A | 0.47 | 12,707 | 0.09 | 0.01 | 4×10−11 | 0.08 | 0.01 | 2×10−12 | 0.08 | 0.01 | 5×10−22 |
| rs12576239 | 11p | intron KCNQ1 | T | 0.13 | 13,211 | 0.12 | 0.02 | 2×10−10 | 0.08 | 0.02 | 3×10−7 | 0.10 | 0.01 | 1×10−15 | |
| rs846111 | 1p | 3′ UTR RNF207 | NPHP4, CHDS, ACOT7, PLEKHG5, KLH21 | C | 0.28 | 6,480 | 0.12 | 0.02 | 1×10−9 | 0.08 | 0.01 | 4×10−9 | 0.10 | 0.01 | 1×10−16 |
| rs4725982 | 7q | downstream KCNH2 | T | 0.22 | 13,706 | 0.09 | 0.02 | 6×10−9 | 0.08 | 0.01 | 1×10−8 | 0.09 | 0.01 | 5×10−16 | |
| rs8049607 | 16p | upstream LITAF | CLEC16A,SNN, ZC3H7A, TNFRSF17 | T | 0.49 | 10,543 | 0.08 | 0.01 | 2×10−8 | 0.07 | 0.01 | 4×10−8 | 0.07 | 0.01 | 5×10−15 |
| rs1805128 | 21q | missense KCNE1 | A | 0.010 | 7644 | 0.48 | 0.09 | 2×10−8 | −0.06 | 0.04 | 0.16 | 0.05 | 0.04 | 0.22 | |
| rs12053903 | 3p | intron SCN5A | C | 0.34 | 13,491 | −0.08 | 0.01 | 3×10−8 | −0.06 | 0.01 | 6×10−8 | −0.07 | 0.01 | 1×10−14 | |
| rs2074518 | 17q | intron LIG3 | RFFL | T | 0.46 | 13,488 | −0.07 | 0.01 | 8×10−8 | −0.05 | 0.01 | 7×10−6 | −0.06 | 0.01 | 6×10−12 |
| rs2968864 | 7q | downstream KCNH2 | C | 0.25 | 12,932 | −0.08 | 0.02 | 1×10−7 | −0.08 | 0.01 | 1×10−9 | −0.08 | 0.01 | 8×10−16 | |