Case–control analysis of all SNPs was performed for the Danish and German population separately, as well as for the combined study population. The substantial number of individuals in the combined study population allowed for the detection of effects as small as OR¼1.2 (for rs2494738, OR¼1.3 due to a smaller minor allele frequency) with a power of at least 87%. Applying an additive model, none of the seven SNPs demonstrated a significant association with longevity in either of the populations (Table 2).

Table 2 Association analysis of AKT1 variations in long-lived individuals

Danish population German population Combined population MAF MAF MAF SNP Sex Cases/controls OR 95% CI P Cases/controls OR 95% CI P Cases/controls OR 95% CI P rs3803304 All 0.25/0.27 0.93 0.80–1.08 0.320 0.27/0.26 1.03 0.91–1.17 0.610 0.26/0.26 0.99 0.90–1.09 0.784 Men 0.25/0.28 0.87 0.69–1.09 0.229 0.28/0.26 1.09 0.84–1.41 0.515 0.26/0.27 0.96 0.81–1.14 0.673 Women 0.25/0.26 0.97 0.80–1.18 0.779 0.26/0.26 1.02 0.88–1.18 0.831 0.26/0.26 1.00 0.89–1.12 0.967 rs2494731 All 0.34/0.34 1.00 0.87–1.17 0.953 0.36/0.35 1.05 0.94–1.17 0.393 0.35/0.34 1.03 0.94–1.13 0.503 Men 0.32/0.35 0.87 0.69–1.11 0.266 0.36/0.33 1.12 0.90–1.39 0.296 0.34/0.34 1.01 0.86–1.18 0.893 Women 0.34/0.32 1.10 0.91–1.34 0.324 0.36/0.35 1.02 0.90–1.17 0.714 0.35/0.34 1.04 0.93–1.16 0.472 rs2494732 All 0.43/0.43 0.99 0.86–1.14 0.879 0.46/0.44 1.06 0.95–1.18 0.296 0.45/0.44 1.04 0.95–1.13 0.406 Men 0.39/0.43 0.81 0.64–1.02 0.073 0.46/0.42 1.13 0.92–1.39 0.253 0.43/0.43 0.99 0.85–1.15 0.928 Women 0.45/0.42 1.12 0.94–1.34 0.214 0.46/0.45 1.03 0.91–1.17 0.594 0.45/0.44 1.06 0.95–1.17 0.287 rs2498796 All 0.30/0.32 0.92 0.79–1.07 0.292 0.32/0.31 1.03 0.92–1.16 0.575 0.31/0.32 0.99 0.90–1.08 0.788 Men 0.29/0.34 0.80 0.63–1.02 0.075 0.33/0.31 1.10 0.88–1.37 0.411 0.31/0.32 0.96 0.81–1.12 0.573 Women 0.30/0.30 1.01 0.83–1.23 0.912 0.32/0.32 1.01 0.88–1.16 0.877 0.31/0.31 1.00 0.90–1.12 0.949 rs2494738 All 0.12/0.12 0.99 0.79–1.23 0.912 0.08/0.07 1.06 0.87–1.29 0.581 0.10/0.09 1.03 0.89–1.19 0.718 Men 0.12/0.13 0.92 0.66–1.29 0.645 0.07/0.07 0.97 0.66–1.44 0.893 0.09/0.11 0.87 0.68–1.12 0.275 Women 0.12/0.12 1.04 0.77–1.39 0.799 0.08/0.07 1.09 0.86–1.38 0.473 0.10/0.09 1.12 0.93–1.34 0.221 rs2494748 All 0.34/0.35 0.95 0.82–1.09 0.466 Men 0.35/0.36 0.96 0.77–1.20 0.728 Women 0.33/0.35 0.94 0.78–1.13 0.510 rs1130214 All 0.31/0.31 1.05 0.91–1.23 0.498 0.30/0.31 0.94 0.83–1.05 0.258 0.30/0.31 0.97 0.89–1.07 0.544 Men 0.32/0.31 1.06 0.83–1.34 0.653 0.28/0.31 0.86 0.69–1.09 0.214 0.30/0.31 0.94 0.79–1.10 0.429 Women 0.31/0.30 1.05 0.86–1.28 0.612 0.31/0.31 0.96 0.84–1.10 0.557 0.31/0.31 0.99 0.89–1.10 0.842

Abbreviations: CI, confidence interval; MAF, minor allele frequency; OR, odds ratio (applying an additive model). Cases are long-lived individuals with an age of 492 years at intake in the Danish population and 495 years in the German population. P-values are uncorrected.

Table 3 Association analysis of AKT1 variations in centenarians

Danish population German population Combined population MAF MAF MAF SNP Sex Cases/controls OR 95% CI P Cases/controls OR 95% CI P Cases/controls OR 95% CI P rs3803304 All 0.23/0.27 0.81 0.61–1.06 0.126 0.26/0.26 1.00 0.86–1.17 0.993 0.26/0.26 0.95 0.83–1.08 0.443 Men 0.16/0.28 0.49 0.26–0.94 0.033 0.26/0.26 1.00 0.70–1.41 0.980 0.25/0.27 0.84 0.63–1.12 0.230 Women 0.24/0.26 0.92 0.67–1.25 0.590 0.26/0.26 1.00 0.84–1.19 0.982 0.26/0.26 0.98 0.85–1.14 0.821 rs2494731 All 0.32/0.34 0.97 0.72–1.30 0.821 0.35/0.35 1.01 0.88–1.16 0.871 0.34/0.34 1.01 0.90–1.15 0.837 Men 0.29/0.35 0.75 0.39–1.42 0.373 0.33/0.33 0.98 0.73–1.31 0.869 0.32/0.34 0.91 0.70–1.18 0.479 Women 0.33/0.32 1.04 0.75–1.44 0.826 0.36/0.35 1.02 0.87–1.20 0.786 0.35/0.34 1.05 0.91–1.20 0.534 rs2494732 All 0.43/0.43 1.01 0.76–1.33 0.957 0.45/0.44 1.03 0.90–1.17 0.684 0.44/0.44 1.03 0.92–1.16 0.580 Men 0.35/0.43 0.69 0.38–1.26 0.224 0.44/0.42 1.05 0.79–1.38 0.741 0.40/0.43 0.97 0.77–1.24 0.830 Women 0.45/0.42 1.12 0.82–1.54 0.468 0.45/0.45 1.02 0.88–1.19 0.776 0.45/0.44 1.05 0.92–1.20 0.454 rs2498796 All 0.28/0.32 0.85 0.63–1.14 0.276 0.32/0.32 0.99 0.86–1.15 0.931 0.31/0.32 0.97 0.85–1.10 0.602 Men 0.27/0.34 0.69 0.37–1.30 0.253 0.31/0.31 1.01 0.75–1.35 0.957 0.30/0.32 0.90 0.70–1.17 0.446 Women 0.28/0.30 0.90 0.64–1.26 0.545 0.32/0.32 0.99 0.84–1.16 0.898 0.31/0.31 0.99 0.86–1.14 0.865 rs2494738 All 0.13/0.12 1.14 0.76–1.72 0.525 0.07/0.07 1.00 0.78–1.29 0.990 0.10/0.09 0.91 0.74–1.12 0.368 Men 0.20/0.13 1.68 0.84–3.38 0.142 0.03/0.07 0.88 0.51–1.54 0.663 0.11/0.11 0.82 0.54–1.24 0.346 Women 0.11/0.12 0.95 0.58–1.57 0.853 0.08/0.07 1.03 0.78–1.37 0.811 0.10/0.09 0.94 0.74–1.20 0.631 rs2494748 All 0.37/0.35 1.11 0.85–1.45 0.443 Men 0.41/0.36 1.23 0.71–2.13 0.457 Women 0.37/0.35 1.08 0.79–1.46 0.643 rs1130214 All 0.33/0.31 1.13 0.84–1.51 0.431 0.29/0.31 0.95 0.83–1.10 0.502 0.31/0.31 0.98 0.87–1.11 0.754 Men 0.30/0.31 0.97 0.54–1.76 0.926 0.28/0.31 0.88 0.64–1.20 0.416 0.31/0.31 0.89 0.69–1.16 0.389 Women 0.33/0.30 1.18 0.84–1.66 0.334 0.31/0.31 0.97 0.83–1.14 0.736 0.31/0.31 1.01 0.88–1.16 0.907

Abbreviations: CI, confidence interval; MAF, minor allele frequency; OR, odds ratio (applying an additive model). Cases are restricted to individuals living to an age of Z100 years. P-values are uncorrected.

approach or taking advantage of the longitudinal data with 412 of follow-up available for the Danish nonagenarian sample.

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