Table 1.
Alleles
|
Per-allele change in heart rateb
|
Stage 1 | Stage 2 | Stages 1 + 2
|
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---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Locus | Chr. | Nearest gene | Annotation | Heart rate SNP | Position (bp)a | Effect | Other | EAF | β | SE | P | P | N | P |
Previously identified heart rate loci | ||||||||||||||
1 | 14 | MYH6 | N,P,S | rs365990 | 22931651 | G | A | 0.353 | 0.564 | 0.047 | 5.66 × 10−26 | 2.19 × 10−21 | 148,972 | 5.39 × 10−45 |
2 | 6 | GJA1 | S | rsl015451 | 122173184 | C | T | 0.102 | 0.713 | 0.072 | 7.06 × 10−20 | 2.14 × 10−17 | 155,303 | 1.14 × 10−32 |
3 | 7 | ACHE | N,Q,S,B | rsl3245899 | 100335067 | G | A | 0.195 | 0.447 | 0.055 | 1.54 × 10−15 | 3.27 × 10−14 | 176,643 | 7.67 × 10−27 |
4 | 1 | CD46 | S,B | rs11118555 | 206007476 | A | T | 0.124 | 0.612 | 0.069 | 4.35 × 10−14 | 7.49 × 10−15 | 166,654 | 3.88 × 10−26 |
5 | 11 | FADS1 | Q,S,B | rsl74549 | 61327958 | A | G | 0.310 | 0.358 | 0.047 | 1.13 × 10−12 | 1.57 × 10−12 | 172,847 | 1.38 × 10−22 |
6 | 6 | SLC35F1 | T,Q,P,S | rslll53730 | 118774215 | T | C | 0.509 | 0.381 | 0.044 | 7.01 × 10−15 | 8.79 × 10−9 | 156,783 | 7.55 × 10−21 |
7 | 12 | LINC00477 (C12orf67) | rsl7287293 | 24662145 | A | G | 0.850 | 0.444 | 0.062 | 6.90 × 10−12 | 3.98 × 10−11 | 151,085 | 3.07 × 10−20 | |
Newly identified heart rate loci | ||||||||||||||
8 | 20 | KIAA1755 | N,S | rs6127471 | 36277452 | C | T | 0.540 | 0.429 | 0.045 | 5.96 × 10−23 | 2.98 × 10−10 | 162,593 | 5.22 × 10−29 |
9 | 2 | CCDC141 | N,P,S | rs17362588 | 179429291 | A | G | 0.114 | 0.736 | 0.077 | 3.25 × 10−18 | 4.22 × 10−11 | 136,061 | 3.57 × 10−26 |
10 | 12 | SYT10 | rs7980799 | 33468257 | A | C | 0.401 | 0.377 | 0.046 | 7.91 × 10−14 | 7.87 × 10−13 | 166,043 | 6.22 × 10−24 | |
11 | 15 | HCN4 | S | rs4489968 | 71452559 | T | G | 0.843 | 0.513 | 0.060 | 8.89 × 10−15 | 3.34 × 10−8 | 160,858 | 3.82 × 10−20 |
12 | 3 | GNB4 | S | rs7612445 | 180655673 | G | T | 0.816 | 0.358 | 0.060 | 2.41 × 10−7 | 7.78 × 10−10 | 140,395 | 1.86 × 10−14 |
13 | 14 | FLRT2 | S | rsl7796783 | 84879664 | T | C | 0.716 | 0.334 | 0.049 | 1.65 × 10−9 | 5.76 × 10−6 | 145,835 | 2.69 × 10−13 |
14 | 7 | CHRM2 | S | rs2350782 | 136293174 | C | T | 0.116 | 0.505 | 0.078 | 1.57 × 10−7 | 2.63 × 10−7 | 131,781 | 1.26 × 10−12 |
15 | 5 | NKX2-5 | Q,S | rs6882776 | 172596769 | G | A | 0.680 | 0.301 | 0.051 | 9.67 × 10−6 | 7.43 × 10−9 | 158,807 | 2.29 × 10−12 |
16 | 7 | GNG11 | C,Q,S,B | rsl80242 | 93387532 | T | A | 0.333 | 0.316 | 0.053 | 7.52 × 10−7 | 5.59 × 10−7 | 148,111 | 6.78 × 10−12 |
17 | 2 | B3GNT7 | N,Q,S,P,B | rsl3030174 | 231979528 | A | C | 0.733 | 0.300 | 0.051 | 1.13 × 10−6 | 3.66 × 10−4 | 144,810 | 1.04 × 10−10 |
18 | 3 | FNDC3B | S | rs9647379 | 173267862 | C | G | 0.400 | 0.206 | 0.047 | 2.59 × 10−7 | 3.07 × 10−4 | 137,314 | 1.17 × 10−9 |
19 | 12 | RFX4 | S | rs2067615 | 105673552 | A | T | 0.490 | 0.278 | 0.044 | 1.05 × 10−7 | 8.49 × 10−4 | 151,197 | 1.58 × 10−9 |
20 | 12 | CPNE8 | rs826838 | 37392998 | C | T | 0.443 | 0.234 | 0.045 | 3.32 × 10−7 | 6.20 × 10−4 | 166,632 | 3.73 × 10−9 | |
21 | 2 | TFPI | N,S | rs4140885 | 188041309 | A | G | 0.317 | 0.217 | 0.049 | 1.85 × 10−6 | 1.40 × 10−3 | 170,395 | 4.72 × 10−8 |
Chr., chromosome. EAF, effect allele frequency based on meta-analysis of stages 1 and 2 combined. Annotation shows whether the heart rate-associated SNP is (i) in strong LD (r2 > 0.8) with a copy number variant (C), nonsynonymous variant (N) or variant in a transcription factor binding site (T); (ii) associated with an eQTL (Q); (iii) expressed at the protein level in mouse heart and phosphorylated upon stimulation of the β1AR (P); (iv) located in or near a gene that was identified as being of potential relevance for heart rate using the automated literature search program SNIPPER (S); or (v) located in or near a biological candidate gene for heart rate (B).
Positions are according to HapMap Build 36, and allele coding is based on the positive strand.
Effect sizes in bpm per effect allele obtained from stage 1 and stage 2 cohorts with heart rate as only outcome (N > 96,790; excludes data from the RRgen Consortium and ERF)