Table 1. Age-Adjusted Baseline Characteristics of Case and Control Participants (mean ± SD)

Parameter Controls Cases p n 374 439 — Biological and physiological phenotypes Height (cm) at Exam 1 163.2 ± 5.4 162.8 ± 5.4 .38 Height (cm) at Exam 4 161.2 ± 5.6 161.3 ± 5.5 .96 Weight (kg) at Exam 1 64.1 ± 9.4 62.0 ± 7.9 .009 Weight (kg) at Exam 4 59.6 ± 9.6 61.6 ± 8.0 .020 BMI (kg/m2) at Exam 1 24.2 ± 3.0 23.5 ± 2.7 .016 BMI (kg/m2) at Exam 4 23.0 ± 3.1 23.6 ± 2.9 .040 BMI at age 25 24.0 ± 3.0 23.4 ± 2.7 .016 Waist:hip ratio 0.95 ± 0.06 0.94 ± 0.05 .015 Systolic BP (mmHg) at Exam 1 135.1 ± 18.8 128.7 ± 18.3 .000 Systolic BP (mmHg) at Exam 4 151.0 ± 26.3 150.4 ± 22.4 .79 Diastolic BP (mmHg) at Exam 1 83.1 ± 11.8 81.2 ± 10.5 .076 Diastolic BP (mmHg) at Exam 4 79.0 ± 12.7 81.6 ± 11.6 .022 EHT (%) >140/90 /meds at Exam 4 74 ± 43 79 ± 41 .24 EHT (%) 160/95 /meds at Exam 4 58 ± 50 57 ± 50 .79 EHT (%) 140/90 /meds at Exam 1 43 ± 49 32 ± 47 .018 EHT (%) 160/95 /meds at Exam 1 26 ± 42 14 ± 37 .0028 ISH (%) SBP>140 at Exam 1 36 ± 47 22 ± 43 .0016 ISH (%) SBP>160 at Exam 1 12 ± 29 3.6 ± 24 .0006 ISH (%) SBP >140 at Exam 4 62 ± 49 66 ± 47 .34 ISH (%) SBP >160 at Exam 4 35 ± 45 31 ± 48 .44 ABI <0.9 (%) 25 ± 38 3.7 ± 28 <.0001 Plasma glucose (mg/dl) 118 ± 37 109 ± 22 .0005 Insulin (mIU/dl) 17.4 ± 15.6 13.8 ± 9.5 .0036 Log insulin (mIU/dl) 2.6 ± 0.6 2.5 ± 0.5 .022 HOMA 5.5 ± 7.1 3.8 ± 3.0 .0008 Total cholesterol (mg/dl) 183 ± 34.2 195 ± 32.6 .0003 HDL cholesterol (mg/dl) 51.3 ± 14.4 51.3 ± 13.1 .97 LDL cholesterol (mg/dl) 105 ± 32.7 114 ± 30.6 .0034 Triglycerides (mg/dl) 146 ± 119 152 ± 79 .54 other clinical phenotypes Poor or fair self-rated health (%) 44 ± 49 25 ± 44 .0001 Coronary heart disease (%) 25 ± 44 13 ± 31 .0014 Stroke history (%) 9.3 ± 27 1.2 ± 15 .0001 Cancer (%) 23 ± 40 7.9 ± 31 .000009 Diabetes (%) 37 ± 48 20 ± 41 .0001 On diabetes medication (%) 18 ± 38 6.9 ± 26 .0003 COPD (emphysema; %) 4.8 ± 21 1.4 ± 12 .038 Physical and cognitive functional phenotypes Grip strength (kg) 26.9 ± 7.1 31.7 ± 5.2 1 × 10–15 Difficulty walking 0.8 km (%) 40 ± 46 6.6 ± 32 1 × 10–17 Cognitive (CASI) score 75.6 ± 19.8 87.1 ± 10.6 2 × 10–14

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notes: The Honolulu Heart Program (HHP) has had 12 full exam cycles since study onset in 1965. Shown are phenotypic variables for long-lived cases and average-lived controls at two exam cycles: HHP Exam 4 (1991–1993), the baseline exam for the present study (ie, when blood was collected for genetic studies and participants were elderly (mean age 76 years; range: 71–93) and Exam 1 (1965–68), when study participants were middle-aged (mean age 54 years; range 45–68). Cases consisted of all Kuakini HHP and Honolulu-Asia Aging Study (HAAS) participants (both living and dead) for which DNA had been collected at Exam 4 and who achieved longevity (age ≥95 years) by June 2011, the follow-up period for this nested case–control study. Data are shown for Exam 4 unless otherwise indicated. ABI = ankle brachial index (ratio of BP in the lower legs to the BP in the arms); BMI = body mass index; BP = blood pressure; CASI = cognitive abilities screening instrument (score range: 1–100); CHD = coronary heart disease; COPD = chronic obstructive pulmonary disease (emphysema); EHT = essential hyper- tension (moderate: systolic/diastolic BP 140–160 mmHg/90–95 mmHg or on antihypertensive medication; severe: systolic/diastolic BP >160/>95 mmHg or on antihypertensive medication); HDL = high-density lipoprotein; HOMA = homeostasis model assessment; ISH = isolated systolic hypertension (moderate: systolic BP 140–160 mmHg; severe: systolic BP >160 mmHg); LDL = low-density lipoprotein.

the percent of chi-square values that fell beyond these limits were actually less than expected: 8.6%, 1.2%, and 0%. For minor allele frequencies of 0.1–0.4 and a nominal signifi- cance level of 0.05, the study had 90% power to detect odds ratios ranging from 1.58–1.95 and 99% power to detect odds ratios of 1.83–2.36. Therefore, although almost all

ancestry. SNPs with at least moderate effects on longevity will create an excess of high chi-square test values. Instead, we noted a deficiency in such values (Tables 2–4). There were 81 χ2 tests for association between genetic variants 2df and case–control status. The quantiles of χ2 for the upper 2df 10, 5, and 1 percentiles are 4.61, 5.99, and 9.21, respectively;

Table 2. Frequency of Minor Allele of Each Tagging SNP of MToR on Chromosome 1p36 in Long-Lived Case vs Control Participants

Total Number of Minor Allele Frequency of SNP ID Position Cases and Controls Cases and Controls, % (95% CI) χ2 p rs1057079 11205058 440/374 12.6 and 12.8 (–0.035 to 0.030) 1.42 .49 rs11581010 11212458 440/374 10.7 and 11.1 (–0.035 to 0.026) 0.36 .84 rs3806317 11248216 440/374 13.8 and 15.2 (–0.049 to 0.019) 0.81 .67 rs11121703 11293792 439/374 13.9 and 15.4 (–0.049 to 0.020) 1.65 .44 rs4845858 11304720 439/372 19.0 and 18.3 (–0.031 to 0.045) 0.63 .73 rs3765904 11321864 440/374 7.3 and 7.4 (–0.026 to 0.025) 1.22 .54

notes: We captured 57 of 57 alleles at r2 ≥ .8, ie, we captured 100% of alleles, and mean of maximum r2 was .97 for the six tagSNPs. CI = confidence interval; SNP = single-nucleotide polymorphism.

Table 3. Frequency of Minor Allele of Each Tagging SNP of RPToR on Chromosome 17p25.3 in Long-Lived Case vs Control Participants