Table Associated with Longevity in 1. SNPs SICS LLIs

SNP CHR Gene Assoc Model a/A MAF p Value OR (95% CI) rs2495513 1 TMEM61 AM G/A 0.2 3.98E-05 0.60 (0.47–0.77) rs4291539 1 — DM C/T 0.42 2.37E-05 1.81 (1.37–2.39) rs10923806 1 — RM G/A 0.38 7.24E-06 2.30 (1.59–3.33) rs1538287 1 KCNH1 DM A/G 0.18 2.64E-05 0.55 (0.42–0.73) rs6540664 1 — AM A/G 0.5 4.45E-05 1.46 (1.22–1.75) rs6701445 1 TAF5L DM T/C 0.15 2.24E-05 1.84 (1.39–2.45) rs12088486 1 — DM A/C 0.28 8.83E-06 0.56 (0.43–0.72) rs10514626 1 — AM A/G 0.06 4.65E-06 0.38 (0.24–0.58) rs7583529 2 CFLAR RM A/G 0.21 6.45E-05 3.15 (1.75–5.68) rs4505466 2 SH3BP4 RM T/C 0.4 8.31E-05 2.06 (1.43–2.96) rs964403 3 SUMF1 RM A/C 0.39 4.91E-05 2.07 (1.45–2.96) rs3864051 3 SUMF1 RM T/C 0.39 5.49E-05 2.07 (1.45–2.96) rs712773 3 GRM7 AM G/A 0.32 4.98E-05 0.66 (0.54–0.81) rs1562688 3 — RM C/A 0.43 4.93E-05 0.50 (0.35–0.70) rs6769400 3 — RM A/G 0.48 1.99E-05 1.91 (1.41–2.57) rs513154 3 IMPG2 DM T/G 0.42 2.14E-06 0.52 (0.39–0.68) rs571391 3 IMPG2 DM G/A 0.43 1.39E-05 0.55 (0.42–0.72) rs2670104 3 — AM C/T 0.36 2.98E-05 0.67 (0.55–0.81) rs10513702 3 — RM T/C 0.48 4.53E-05 1.85 (1.37–2.48) rs2354314 4 — RM T/C 0.43 7.81E-05 0.51 (0.36–0.71) rs795602 4 MGST2 AM T/C 0.47 2.11E-05 0.67 (0.56–0.81) rs4282145 4 — RM T/G 0.33 5.32E-05 0.38 (0.23–0.62) rs11738302 5 — DM T/C 0.27 3.81E-05 0.57 (0.44–0.75) rs888808 5 RHOBTB3 AM G/A 0.41 1.94E-05 0.67 (0.55–0.80) rs10491334 5 CAMKIV DM T/C 0.18 2.88E-05 0.55 (0.42–0.73) rs1428689 5 — RM C/T 0.49 5.51E-05 1.85 (1.37–2.49) rs697739 6 ATXN1 DM A/G 0.34 5.05E-05 0.59 (0.45–0.76) rs9366292 6 — AM G/A 0.25 4.26E-05 0.64 (0.52–0.79) rs1563301 6 — DM G/A 0.13 1.22E-05 0.50 (0.37–0.69) rs10277343 7 — AM T/G 0.28 1.79E-05 0.64 (0.52–0.78) rs4727899 7 — DM G/A 0.48 4.37E-05 0.55 (0.41–0.73) rs846427 7 — RM A/G 0.45 3.82E-05 1.94 (1.41–2.67) rs4574762 7 — RM G/A 0.26 2.29E-06 0.19 (0.09–0.41) rs7842001 8 — RM G/A 0.26 7.12E-05 0.32 (0.18–0.58) rs3134204 8 — AM G/A 0.28 4.83E-05 1.51 (1.24–1.85) rs1484583 8 — AM T/G 0.27 3.74E-05 1.53 (1.25–1.88) rs3102484 8 — RM G/A 0.49 9.20E-05 1.82 (1.35–2.47) rs10956502 8 FAM49B DM G/T 0.31 2.25E-05 0.57 (0.44–0.74) rs2905476 9 — RM T/C 0.28 6.35E-05 0.29 (0.15–0.55) rs7873259 9 ANKRD19 RM G/A 0.27 1.18E-05 3.14 (1.84–5.37) rs4740391 9 — AM G/A 0.11 3.99E-05 0.52 (0.38–0.71) rs12413082 10 MSRB2 DM T/C 0.32 1.50E-06 0.53 (0.41–0.69) rs7915479 10 CDH23 DM T/C 0.47 1.47E-05 1.92 (1.43–2.59) rs1556758 10 SORCS1 RM C/T 0.45 3.47E-05 0.50 (0.36–0.70) rs2073586 11 ABCC8 RM T/C 0.4 8.15E-05 0.48 (0.33–0.69) rs11237644 11 — AM A/G 0.4 9.24E-06 1.52 (1.26–1.83) rs870959 11 — AM T/C 0.40 1.27E-05 1.51 (1.25–1.81) rs6592810 11 — AM C/T 0.33 1.10E-05 1.54 (1.27–1.86) rs4938180 11 IGSF4 RM T/C 0.49 2.16E-05 1.91 (1.41–2.58) rs2111173 12 PTPRO DM C/T 0.39 5.22E-05 1.74 (1.33–2.28) rs969845 12 — RM A/G 0.18 7.22E-05 5.87 (2.19–15.70) rs9315385 13 DCAMKL1 AM G/T 0.14 3.98E-05 1.74 (1.33–2.26) rs2147556 13 — AM T/C 0.29 9.59E-06 0.63 (0.52–0.78) rs731287 13 — RM T/C 0.28 9.88E-05 2.51 (1.56–4.05) rs285097 13 RNF113B AM G/T 0.08 3.79E-05 0.47 (0.33–0.68) rs1584547 14 — RM T/C 0.24 8.52E-05 2.96 (1.69–5.21) rs4594173 14 MADMC1 AM G/A 0.08 4.88E-05 1.94 (1.40–2.69) rs2277472 14 MAMDC1 AM T/C 0.09 3.88E-05 1.95 (1.41–2.70) rs10134056 14 — RM A/G 0.39 5.61E-05 0.46 (0.31–0.68) rs4777170 15 — RM C/T 0.43 4.52E-05 2.00 (1.43–2.80) rs81647 16 — DM G/A 0.4 5.53E-05 0.58 (0.44–0.76) rs1582594 16 — DM A/C 0.32 3.00E-06 1.87 (1.44–2.43)

Table ontinued 1. (C )

SNP CHR Gene Assoc Model a/A MAF p Value OR (95% CI) rs2967137 16 — DM C/T 0.37 8.00E-06 1.83 (1.40–2.38) rs6504441 17 PRKCA AM T/C 0.3 1.06E-06 0.60 (0.49–0.74) rs2070325 20 LPLUNC4 RM G/A 0.3 5.98E-05 2.42 (1.56–3.77) rs130329 22 — RM A/C 0.47 3.52E-05 0.50 (0.36–0.7) rs135416 22 — DM T/C 0.44 4.86E-05 0.57 (0.43–0.75)

SNP, single-nucleotide polymorphism; CHR, chromosome; Gene, official gene symbol; Assoc Model, associated genetic model (AM: allelic model [1 df]), DM, dominant model [1, df]; RM, recessive model [1 df]); a/A, minor allele/major allele based on whole samples; MAF, minor allele frequency; OR, odds ratio; 95% CI, confidence interval. For example, subjects who carry the allele G for rs2495513 (allelic model) have 0.60 times the odds for longevity compared to subjects who carry allele A.

95% CI 0.32–0.90; p¼ 5.73(cid:2)10(cid:3)5) (Supplementary Table 4). Because haplotypes did not add information with respect to rs10491334, we decided to evaluate a single SNPs approach for the replication phase.

Univariate chi-squared-based association tests identified 67 SNPs showing genomic control adjusted p< 1(cid:2)10(cid:3)4 (Ta- ble 1). Many of these SNPs mapped to the genes of proteins potentially relevant to the aging process (Table 1, Supple- mentary Table 2, Supplementary Figs. 3 and 4); for example, potassium voltage-gated channel, subfamily H (age related), member 1 gene (KCNH1), also known as EAG1 or K(V)10.1, is an important regulator of cell proliferation under the control of IGF-1 signaling.30 None of these associations was signifi- cantly influenced by gender-confounding effects or by po- tential gender-specific associations (Supplementary Table 3).