Table 1.
59 variants independently associated with telomere length, mapping to 36 loci, in 109,122 ancestrally diverse (African, European, Hispanic/Latino, Asian) individuals from TOPMed
| Single variant analysis in pooled trans-population sample |
p values from joint model |
Effect sizes from joint model |
Cochran’s Q (p value) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chr | Locus | SNP | Prior GWAS | Annotation | MAC | p value | Percent variation explained | Trans- population | European | African | Hispanic/ Latino | Asian | Trans- population | European | African | Hispanic/ Latino | Asian | |
| 1 | ZMYM4 | rs11581846 | 7 | 87500 | 3.04E−10 | 0.036% | 1.74E−11 | 7.99E−5 | 8.80E−3 | 3.37E−6 | 4.13E−1 | −19.9 | −21.1 | −15.0 | −24.6 | −8.7 | 0.44 | |
| 1 | BCL2L15 | rs2296176 | 7 | 33274 | 2.84E−10 | 0.036% | 1.52E−10 | 6.57E−8 | 2.38E−3 | 3.16E−1 | 2.07E−2 | −19.5 | −22.4 | −22.0 | −7.3 | −26.9 | 0.28 | |
| 1 | PARP1 | rs1136410 | Known | missense | 36395 | 9.32E−20 | 0.076% | 9.14E−22 | 6.10E−9 | 1.02E−2 | 7.51E−7 | 2.04E−4 | −29.3 | −26.0 | −23.7 | −29.5 | −32.5 | 0.87 |
| 2 | ACYP2 | rs17189743 | Known | missense | 3741 | 7.18E−12 | 0.043% | 4.24E−11 | 2.70E−6 | 2.52E−1 | 5.20E−6 | 1.94E−1 | −55.4 | −50.7 | −30.4 | −82.4 | −46.8 | 0.34 |
| 2 | rs144980386 | deletion | 28773 | 1.32E−17 | 0.067% | 1.99E−17 | 7.78E−13 | 7.32E−4 | 1.45E−4 | 6.78E−1 | 27.5 | 33.6 | 21.2 | 30.5 | 4.8 | 0.08 | ||
| 3 | LINC00901 | rs961617801 | 6 | 12 | 1.25E−11 | 0.042% | 4.81E−11 | 2.82E−10 | – | – | – | 1009.6 | 1038.5 | – | – | – | – | |
| 3 | TERC | rs12637184 | Known | 4 | 47452 | 1.30E−96 | 0.399% | 1.58E−103 | 1.02E−50 | 1.84E−15 | 7.32E−30 | 2.33E−11 | −59.8 | −57.0 | −65.8 | −66.1 | −57.3 | 0.51 |
| 3 | rs9826466 | N/A | 4066 | 3.25E−17 | 0.065% | 3.66E−21 | 2.04E−01 | 7.28E−19 | 2.96E−03 | – | −77.0 | 253.9 | −77.6 | −77.8 | – | 0.25 | ||
| 3 | P3H2 | rs10937417 | 7 | 80209 | 6.89E−10 | 0.035% | 1.89E−10 | 9.04E−5 | 1.65E−5 | 2.33E−3 | 6.30E−1 | 14.6 | 13.5 | 17.9 | 17.1 | −4.4 | 0.16 | |
| 4 | SLC2A2 | rs4235345 | 6 | 44302 | 3.82E−9 | 0.032% | 1.88E−9 | 3.24E−7 | 4.39E−2 | 1.86E−2 | 5.70E−2 | 16.8 | 19.8 | 12.8 | 13.2 | 47.1 | 0.41 | |
| 4 | NAF1 | rs60735607∗ | Known | 6 | 57418 | 0.003964 | 0.008% | 4.43E−12 | 4.45E−7 | 7.20E−3 | 5.33E−4 | 9.94E−1 | −18.5 | −20.0 | −12.9 | −22.4 | −0.1 | 0.43 |
| 4 | rs113580095 | 7 | 290 | 4.72E−18 | 0.069% | 1.63E−16 | 2.57E−8 | 7.12E−2 | 3.40E−7 | – | −254.7 | −231.9 | −287.8 | −257.9 | – | 0.89 | ||
| 4 | rs1351222 | 7 | 50104 | 3.27E−26 | 0.103% | 1.60E−32 | 9.04E−16 | 1.50E−7 | 6.80E−11 | 6.58E−3 | 32.7 | 32.7 | 28.9 | 41.2 | 28.9 | 0.49 | ||
| 5 | TERT | rs192999400 | Known | 5 | 2470 | 3.10E−15 | 0.057% | 8.21E−23 | 2.15E−1 | 3.90E−17 | 3.42E−3 | 6.19E−2 | 101.3 | 88.7 | 97.4 | 96.9 | 108.4 | 1.00 |
| 5 | rs6897196 | 5 | 102081 | 1.87E−83 | 0.344% | 6.04E−13 | 7.24E−4 | 7.90E−8 | 1.87E−2 | 1.46E−1 | 20.8 | 16.2 | 25.2 | 16.8 | 23.4 | 0.55 | ||
| 5 | rs7705526∗∗ | 7 | 64162 | 1.64E−92 | 0.382% | 2.01E−18 | 1.16E−11 | 7.73E−4 | 1.46E−3 | 6.47E−2 | 30.0 | 35.5 | 22.5 | 27.1 | 34.1 | 0.47 | ||
| 5 | rs2853677∗∗ | 5 | 80905 | 8.17E−65 | 0.265% | 1.25E−19 | 9.27E−7 | 8.88E−10 | 1.33E−5 | 8.34E−2 | −23.9 | −17.7 | −33.9 | −28.9 | −22.0 | 0.08 | ||
| 5 | rs34052286 | 3a | 6173 | 1.50E−12 | 0.046% | 5.47E−22 | 3.86E−1 | 1.09E−14 | 2.39E−5 | – | −66.0 | −59.3 | −61.6 | −74.3 | – | 0.80 | ||
| 5 | rs114616103∗ | 7 | 4527 | 2.39E−7 | 0.024% | 2.03E−13 | 1.44E−9 | 2.09E−2 | 1.72E−2 | 4.93E−1 | −57.2 | −59.2 | −37.9 | −57.6 | −71.9 | 0.73 | ||
| 5 | CXXC5 | rs75903170 | 2b | 11895 | 5.69E−10 | 0.035% | 7.01E−10 | 2.83E−4 | 2.58E−6 | 8.14E−2 | 4.31E−1 | 29.6 | 25.5 | 46.7 | 22.3 | 12.6 | 0.19 | |
| 6 | HSPA1A | rs1008438 | 2b | 106908 | 3.42E−17 | 0.065% | 6.64E−19 | 3.61E−9 | 1.40E−4 | 4.10E−7 | 1.71E−2 | −20.3 | −19.7 | −18.4 | −25.7 | −20.5 | 0.73 | |
| 7 | POT1 | rs720613 | Known | 7 | 62325 | 1.27E−26 | 0.105% | 1.37E−27 | 2.59E−18 | 5.87E−6 | 3.63E−5 | 2.51E−2 | −26.3 | −31.3 | −20.4 | −24.6 | −21.0 | 0.26 |
| 7 | rs202187871 | missense | 27 | 4.89E−12 | 0.044% | 6.72E−13 | 6.42E−12 | – | – | – | 738.3 | 719.6 | – | – | – | – | ||
| 7 | TNP03 | rs7783384 | 5 | 92528 | 2.34E−12 | 0.045% | 6.10E−12 | 1.22E−7 | 1.47E−3 | 2.54E−2 | 2.04E−2 | −15.2 | −17.8 | −13.3 | −11.4 | −19.8 | 0.64 | |
| 8 | TERF1 | rs183633026 | Known | 7 | 1132 | 1.59E−10 | 0.038% | 1.45E−10 | 3.48E−2 | 7.67E−1 | 1.51E−9 | – | 99.4 | 75.4 | −22.0 | 109.6 | – | 0.18 |
| 8 | rs73687065 | 5 | 1676 | 3.10E−12 | 0.045% | 8.10E−12 | 7.74E−1 | 2.76E−10 | 5.71E−3 | – | 85.3 | 24.9 | 87.4 | 97.0 | – | 0.74 | ||
| 8 | rs10112752 | 7 | 78968 | 4.59E−13 | 0.048% | 9.83E−12 | 5.13E−9 | 5.69E−3 | 4.16E−2 | 2.83E−2 | −15.8 | −19.2 | −12.6 | −11.2 | −26.2 | 0.40 | ||
| 10 | NOC3L | rs3758526 | missense | 32511 | 6.80E−12 | 0.043% | 5.77E−13 | 1.63E−5 | 2.70E−5 | 1.38E−2 | 1.42E−2 | −22.0 | −21.1 | −22.6 | −19.8 | −23.1 | 0.99 | |
| 10 | NKX2-3 | rs10883359 | 7 | 54905 | 3.60E−12 | 0.044% | 9.34E−11 | 5.46E−5 | 5.14E−6 | 3.46E−2 | 1.70E−1 | −16.5 | −14.5 | −28.1 | −11.9 | −11.9 | 0.19 | |
| 10 | OBFC1 | rs10883948 | Known | 7 | 94489 | 2.04E−34 | 0.137% | 3.97E−12 | 1.20E−5 | 3.99E−4 | 2.18E−2 | 6.42E−4 | −18.8 | −15.7 | −24.2 | −13.9 | −46.8 | 0.11 |
| 10 | rs112163720∗ | 4 | 15559 | 0.440005 | 0.001% | 4.86E−16 | 9.57E−7 | 4.34E−7 | 3.69E−4 | 9.38E−4 | 37.1 | 48.1 | 39.1 | 35.3 | 54.9 | 0.66 | ||
| 10 | rs9420907∗∗ | 3a | 54838 | 3.90E−83 | 0.342% | 6.80E−54 | 3.65E−18 | 6.94E−19 | 6.79E−13 | 9.41E−1 | −49.2 | −44.3 | −52.4 | −53.8 | −2.4 | 0.30 | ||
| 10 | rs111447985 | 2a | 2391 | 2.29E−24 | 0.095% | 3.03E−35 | 4.94E−3 | 2.24E−2 | 5.44E−22 | 2.81E−10 | 131.9 | 120.7 | 98.1 | 143.4 | 137.2 | 0.77 | ||
| 11 | ATM | rs61380955 | Known | 7 | 105969 | 2.47E−17 | 0.066% | 1.11E−18 | 5.79E−14 | 2.97E−4 | 2.47E−3 | 9.19E−2 | −19.6 | −24.8 | −15.6 | −15.7 | −14.6 | 0.24 |
| 13 | KBTBD7 | rs1411041 | 6 | 85572 | 6.29E−14 | 0.052% | 6.65E−15 | 1.46E−8 | 6.04E−4 | 1.13E−3 | 1.77E−2 | 22.4 | 25.5 | 20.5 | 20.2 | 20.8 | 0.87 | |
| 14 | TINF2 | rs28372734 | Known | 4 | 2648 | 1.74E−27 | 0.108% | 1.27E−30 | 4.91E−2 | 3.42E−6 | 4.59E−9 | 7.26E−10 | 112.6 | 120.9 | 103.9 | 132.1 | 94.8 | 0.59 |
| 14 | rs8016076 | 2b | 1977 | 1.80E−11 | 0.041% | 4.46E−13 | 1.01E−1 | 1.70E−10 | 6.73E−3 | – | 83.8 | 374.8 | 80.9 | 87.5 | – | 0.43 | ||
| 14 | rs41293824 | 5 | 1543 | 1.31E−9 | 0.034% | 1.87E−10 | 7.43E−1 | 1.83E−7 | 2.58E−4 | – | 83.1 | 40.9 | 76.5 | 125.7 | – | 0.40 | ||
| 14 | DCAF4 | rs2572 | Known | 5 | 20731 | 5.14E−12 | 0.044% | 6.70E−14 | 2.00E−7 | 1.07E−4 | 3.42E−3 | 1.75E−3 | 28.0 | 27.7 | 36.5 | 25.5 | 33.8 | 0.80 |
| 15 | ATP8B4 | rs7172615 | 4 | 41027 | 4.31E−9 | 0.032% | 3.53E−10 | 1.14E−7 | 3.77E−3 | 1.96E−1 | 1.90E−1 | −17.8 | −20.3 | −21.4 | −8.7 | −12.0 | 0.41 | |
| 16 | TERF2 | rs9925619 | Known | 7 | 66224 | 3.01E−14 | 0.053% | 7.84E−15 | 3.03E−4 | 1.01E−7 | 1.02E−6 | 5.10E−1 | 18.6 | 13.1 | 22.5 | 27.9 | 8.9 | 0.10 |
| 16 | CLEC18C | rs62049363 | 7 | 61724 | 4.09E−10 | 0.036% | 3.25E−11 | 5.24E−7 | 1.44E−1 | 4.80E−4 | 3.52E−1 | −16.8 | −16.7 | −11.2 | −19.4 | −8.5 | 0.69 | |
| 16 | RFWD3 | rs7193541 | Known | missense | 93079 | 1.47E−16 | 0.063% | 3.18E−17 | 3.39E−12 | 5.63E−5 | 1.66E−3 | 5.21E−1 | −18.7 | −22.9 | −16.8 | −16.9 | −5.6 | 0.24 |
| 16 | MPHOSPH6 | rs2967355 | Known | 6 | 34993 | 3.96E−19 | 0.073% | 2.04E−20 | 2.69E−11 | 1.58E−4 | 4.86E−7 | 9.91E−1 | −28.2 | −26.2 | −33.8 | −36.8 | −0.1 | 0.05 |
| 16 | BANP | rs12934497 | 5 | 77109 | 9.15E−10 | 0.034% | 8.16E−0 | 1.53E−5 | 1.62E−3 | 5.66E−3 | 1.15E−1 | 14.6 | 14.1 | 15.2 | 15.2 | 31.8 | 0.86 | |
| 18 | TYMS | rs150119891∗ | 5 | 1320 | 2.27E−7 | 0.025% | 1.92E−11 | 3.69E−10 | 2.80E−1 | 2.89E−3 | – | −98.8 | −104.9 | −52.3 | −160.9 | – | 0.32 | |
| 18 | rs8088781 | 5 | 25774 | 2.49E−15 | 0.057% | 8.91E−32 | 2.78E−15 | 1.75E−8 | 8.74E−9 | 8.66E−2 | −50.6 | −56.0 | −40.8 | −59.3 | −160.9 | 0.21 | ||
| 18 | rs2612101∗ | 5 | 56194 | 0.407696 | 0.001% | 6.29E−16 | 7.76E−7 | 2.11E−4 | 5.13E−8 | 3.89E−2 | 26.0 | 29.4 | 18.4 | 35.1 | 171.4 | 0.05 | ||
| 18 | SETBP1 | rs2852770 | 7 | 46513 | 1.00E-11 | 0.042% | 1.15E-12 | 2.32E-09 | 4.37E-02 | 1.23E-04 | 7.01E-01 | −19.0 | −25.1 | −9.4 | −24.3 | −4.1 | 0.03 | |
| 19 | ZNF257/ZNF676 | rs8105767∗∗ | Known | 6 | 76591 | 3.59E−18 | 0.069% | 1.52E−18 | 6.32E−9 | 1.14E−7 | 5.00E−3 | 5.14E−3 | 20.3 | 20.8 | 22.2 | 15.0 | 25.5 | 0.68 |
| 20 | SAMHD1 | rs2342113 | 6 | 51830 | 4.62E−18 | 0.069% | 1.58E−19 | 2.50E−13 | 4.00E−4 | 1.34E−6 | 3.67E−1 | −23.7 | −33.8 | −16.1 | −27.4 | −7.7 | 0.01 | |
| 20 | RTEL1 | rs41308088 | Known | 5 | 14105 | 1.58E−10 | 0.038% | 8.42E−16 | 6.46E−15 | 6.24E−2 | 4.61E−2 | 2.05E−1 | 37.1 | 45.3 | 25.1 | 20.1 | 58.1 | 0.12 |
| 20 | rs79981941 | 6 | 21592 | 1.46E−23 | 0.092% | 1.37E−12 | 5.06E−6 | 4.73E−3 | 5.48E−6 | 9.09E−2 | −26.7 | −26.4 | −18.6 | −39.1 | −47.5 | 0.25 | ||
| 20 | rs41309367∗∗ | 5 | 71377 | 2.52E−33 | 0.133% | 1.01E−42 | 5.92E−23 | 1.49E−15 | 9.58E−9 | 6.05E−1 | −34.1 | −37.0 | −38.0 | −33.0 | −5.1 | 0.02 | ||
| 20 | rs35640778 | missense | 2354 | 2.31E−28 | 0.112% | 1.47E−38 | 3.77E−29 | 2.06E−7 | 1.11E−4 | 9.25E−1 | −140.5 | −141.8 | −176.3 | −116.7 | 13.8 | 0.42 | ||
| 20 | rs181080831 | synonymous | 675 | 6.40E−17 | 0.064% | 7.53E−19 | 8.00E−18 | 8.50E−1 | 1.39E−2 | – | 180.5 | 199.5 | 15.5 | 133.0 | – | 0.07 | ||
| 22 | TYMP | rs361725 | 3a | 101750 | 1.36E−10 | 0.038% | 8.26E−12 | 3.97E−11 | 2.32E−1 | 4.11E−2 | 2.39E−2 | −15.6 | −22.1 | −5.4 | −10.6 | −21.2 | 0.02 | |
| X | VSIG4 | rs12394264 | 4 | 50912 | 9.67E−16 | 0.059% | 5.36E−17 | 1.57E−7 | 1.94E−5 | 4.13E−5 | 7.28E−1 | 19.0 | 19.2 | 15.7 | 20.6 | 13.3 | 0.85 | |
| X | GAB3 | rs2728723 | 5 | 63517 | 1.21E−12 | 0.046% | 3.47E−12 | 4.45E−8 | 8.67E−2 | 7.96E−4 | 4.55E−2 | 13.2 | 15.7 | 6.0 | 14.4 | 17.0 | 0.17 | |
Loci are labeled as known if the sentinel variants in the locus were in LD (r2 ≥ 0.7) with previously reported GWAS association for telomere length. There are 5 variants marked with an asterisk where the primary analysis did not meet our threshold of p < 5 × 10−9; however, they reached significance after conditioning on significant variants mapping to the chromosome (detailed in Table S2). Variants marked with a double asterisk are direct matches to prior reported sentinel variants. Percentage of trait variation explained by each variant is provided from single-variant association tests. p values and effect sizes (in base pairs) are reported from a joint model including all variants. p values for effect heterogeneity across population groups were generated using Cochran’s Q statistic. MAC is the minor allele count from the full combined sample. For all exonic variants, detailed annotation is provided, while for all non-coding variants, the RegulomeDB score is given.