Table 1.
Overview of Genome‐Wide Association Studies Used as Instrumental Variables
| Risk factor (reference) | Cohort(s) | Measurement unit* | Sample size | Ancestry |
No. SNPs (MVP/GoLEAD‐SUMMIT) of total identified |
% Variance explained | F‐statistic |
Sample overlap MVP |
Sample overlap GoLEAD‐SUMMIT |
|---|---|---|---|---|---|---|---|---|---|
| Glucose metabolism | |||||||||
| Type 2 diabetes 27 | Meta‐analysis >30 cohorts | Odds of type 2 diabetes | 898 130 | European | 280/281 of 403 | 16.3% for 403 SNPs | 165 | none | 96% |
| Fasting glucose 28 | MAGIC Consortium (new data meta‐analyzed with 4 existing GWASs) | mmol/L | 133 010 | European | 35/35 of 36 | 4.8% For 36 SNPs | 350 | none | 0.5% |
| Lipid metabolism | |||||||||
| LDL‐C 29 | Meta‐analysis >40 cohorts | 1 SD increase in LDL‐C | 188 577 | Predominantly European | 53/54 of 58 | 14.6% for 58 SNPs | 784 | none | 5% |
| HDL‐C 29 | Meta‐analysis >40 cohorts | 1 SD increase in HDL‐C | 188 577 | Predominantly European | 65/65 of 71 | 13.7 for 71 SNPs | 593 | none | 5% |
| Triglycerides 29 | Meta‐analysis >40 cohorts | 1 SD increase in triglycerides | 188 577 | Predominantly European | 35/35 of 40 | 11.7% for 40 SNPs | 920 | none | 5% |
| Smoking | |||||||||
| Smoking initiation 30 | GSCAN Consortium (>30 cohorts) | Ever smoked regularly compared with never smoked | 1 232 091 | European | 346/360 of 378 | 2.3% for 378 SNPs | 17 | none | 31% |
| Smoking cessation 30 | GSCAN Consortium (>30 cohorts) | Current compared with former smokers | 547 219 | European | 21/21 of 24 | 0.1% For 24 SNPs | 11 | none | 42% |
| Smoking heaviness/cigarettes per day 30 |
GSCAN Consortium (>30 cohorts) |
SD increase in number of cigarettes smoked daily | 337 334 | European | 45/47 of 55 | ≈1% for 55 SNPs | 55 | none | 88% |
| Diet | |||||||||
| Alcohol consumption 30 | GSCAN Consortium (>30 cohorts) | SD of log‐transformed alcoholic drinks/week | 941 280 | European | 84/90 of 99 | ≈0.2% for 99 SNPs | 5.8 | none | 75% |
| Coffee consumption 31 | UK Biobank; Nurses' Health Study; Health Professionals Follow‐Up Study; Women's Genome Health Study | 50% increase | 375 833 (374 046 for rs117692895) | European | 14/14 of 15 | 0.48% for 15 SNPs | 84 | none | 90% |
| Physical activity | |||||||||
| Physical activity, MVPA 32 | UK Biobank | SD increase in MET‐minutes /wk of MVPA | 377 234 | European | 7/7 of 9 | 0.073% for 9 SNPs† | 25 | none | 82% |
| Sedentary behavior 33 | UK Biobank | SD increase in sedentary time | 91 105 | European | 4/4 of 4 | 0.08% for 4 SNPs | 48 | none | 20% |
| Sleep | |||||||||
| Insomnia 34 | UK Biobank; 23 and Me | Odds of Insomnia | 1 331 010 | European | 229/238 of 248 | 2.6% for 248 SNPs | 28 | none | 84% |
| Sleep duration 35 | UK Biobank | H/d | 446 118 | European | 75/78 of 78 | 0.69% for 78 SNPs | 23 | none | 90% |
| Long sleep duration 35 | UK Biobank | ≥9 h compared with 7–8 h/d | 446 118 | European | 7/7 of 8 | Not available | Not available | none | 74% |
| Short sleep duration 35 | UK Biobank | <7 h compared with 7–8 h /d | 446 118 | European | 27/26 of 27 | Not available | Not available | none | 89% |
| Education | |||||||||
| Education level 36 | Meta‐analysis >70 cohorts | 1 SD increase in years of educational attainment | 1 131 881 | European | 1155/1201 of 1271 | 11–13% for 1271 SNPS | 29 | none | 90% |
GSCAN indicates GWAS and Sequencing Consortium of Alcohol and Nicotine Use; GWAS, Genome‐wide association study; HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; MAGIC, Meta‐Analysis of Glucose and Insulin related traits Consortium; MET, metabolic equivalent of task; MVP, Million Veteran Program; MVPA, moderate to vigorous physical activity; and SNP, single nucleotide polymorphism.
Units as used in this Mendelian randomization study.
Not reported, calculated using the formula: r2=2×Minor Allele Frequency×(1 – Minor Allele Frequency)×(beta/SD)2.