Table 3.
Results of included studies investigating diabetes related and other endocrine factors, and telomere length
| Study Exposure (analytic n/casesa) | Methods | Results MR estimate (95% CI) |
|---|---|---|
| Østergaard et al., 2015 [12] T2D, fasting glucose, insulin resistance (54,162 / 17,008) |
Inverse-variance weighted combination of summary statisticsb |
AD IV estimated OR per unit in log odds of T2D = 1.02 (0.97, 1.07), p = 0.535 IV estimated OR per fasting glucose SD = 1.12 (0.97, 1.30), p = 0.112c IV estimated OR per log-fasting insulin SD = 1.32 (0.88, 1.98), p = 0.177> |
| Walter et al., 2016 [21] T2D (dementia probability: 8,501; AD: 54,162 / 17,008) |
GRS is weighted sum of risk alleles converted to a probability predicting dementia probability (logit) T2D GRS R2 = 1.98% adiposity GRS R2 = 0.09% β-cell function GRS R2 = 1.28% insulin sensitivity GRS R2 = 0.29% other GRS R2 = 0.30%; 2SLS regression for dementia probabilityd; inverse-variance weighted combination of summary statistics for AD |
Dementia probability (logit) IV estimated change per predicted risk of T2D = 0.04 (−0.92, 1.01) IV estimated change per predicted risk of T2D (adiposity SNPs) = 2.23 (−2.12, 6.59) IV estimated change per predicted risk of T2D (β-cell function SNPs) = −0.49 (−1.70, 0.73) IV estimated change per predicted risk of T2D (insulin sensitivity SNPs) = 1.59 (−0.99, 4.18) IV estimated change per predicted risk of T2D (other SNPs) = 0.21 (−2.28, 2.71) AD IV estimated OR per unit in log odds of T2D = 1.01 (0.96, 1.06), p = 0.79 IV estimated OR per unit in log odds of T2D (adiposity SNPs) = 0.93 (0.74, 1.15), p = 0.49 IV estimated OR per unit in log odds of T2D (β-cell function SNPs) = 1.00 (0.94, 1.07), p = 0.89 IV estimated OR per unit in log odds of T2D (insulin sensitivity SNPs) = 1.17 (1.02, 1.34), p = 0.02e IV estimated OR per unit in log odds of T2D (other SNPs) = 0.90 (0.79, 1.04), p = 0.14 |
| Kueider et al., 2016 [20] Vitamin D (848) |
GRS is sum of minor alleles; 2SLS regressionf |
Global cognition IV estimated change per ng/mL of 25(OH)D = 0.01 (−0.01, 0.06), p = 0.41 |
| Mokry et al., 2016 [23] Vitamin D (54,162 / 17,008) |
Inverse-variance weighted combination of summary statistics; R2 = 2.44% |
AD IV estimated OR per SD decrease in natural log 25(OH)D = 1.25 (1.03, 1.51), p = 0.02g IV estimated OR per SD decrease in natural log 25(OH)D (metabolism SNPs) = 1.46 (1.03, 2.07), p = 0.03 IV estimated OR per SD decrease in natural log 25(OH)D (synthesis SNPs) = 1.17 (0.93, 1.46), p = 0.17 |
| Zhao et al., 2016 [22] Testosterone (4,122) |
2SLS regression; R2 = 4.1% |
Global cognition IV estimated change per testosterone nmol/L = 0.06 (−0.002, 0.12), p = 0.06 |
| Au Yeung et al., 2016 [24] 17β-estradiol (3,066) |
Ratio of coefficients; R2 = 4.9%; |
Global cognition IV estimated change per log 17β-estradiol pmol/L = 0.39 (−0.87, 1.65) |
| Zhan et al., 2016 [25] Telomere length (54,162 / 17,008) | Inverse-variance weighted combined summary statistics |
AD IV estimated OR per SD decrease of telomere length = 1.36 (1.12, 1.67), p = 0.002 |
AD, Alzheimer’s disease; CI, confidence interval; GRS, genetic risk score; MR, Mendelian randomization; OR, odds ratio; SD, standard deviation; SNP, single nucleotide polymorphism; T2D, type 2 diabetes; 2SLS, two-stage least squares; 25(OH)D, 25-hydroxyvitamin D. aReported for binary outcomes only. bStudy applied a Bonferroni corrected significance threshold of p < 3.8×10−3. cIV estimated OR per fasting glucose SD = 1.19; 95% CI: 1.03–1.37, p = 0.02 after exclusion of 1 SNP associated with AD. dAdjusted for age, sex and 6 population eigenvectors in analyses of dementia probability. eBonferroni corrected p = 0.08. fAdjusted for age, sex, education, apolipoprotein E ɛ4 status, depressive symptoms, body mass index, and season of 25(OH)D collection. gIV estimated OR per SD decrease in natural log 25(OH)D = 1.19 (0.96, 1.45), p = 0.11 and 1.26 (1.00, 1.60), p = 0.05 after exclusion of rs2282679 due to potential pleiotropic effects and rs12785878 as an ancestry marker, respectively.