Table 2.
Examples of MR studies using fracture as an outcome.
| Exposure | Sample source for exposure data | Genetic variants (n) | Outcome | Sample size and data sources for the outcome data | MR method | Evidence of causal effect (Yes/No) | References |
|---|---|---|---|---|---|---|---|
| Decreased FN BMD | Europeans | 43 | Fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports | 147,200 cases and 150,085 controls (primarily of European ancestry) | Two-sample (IVW) | Yes | (19) |
| Decreased LS BMD | 40 | Yes | |||||
| Earlier menopause | 54 | No | |||||
| Rheumatoid arthritis | 30 | No | |||||
| Inflammatory bowel disease | 19 | No | |||||
| Type 1 diabetes | 151 | No | |||||
| Decreased THS | 20 | No | |||||
| Homocysteine | 13 | No | |||||
| Decreased Grip strength | 15 | Yes | |||||
| Late puberty | 106 | Some evidence | |||||
| Fasting glucose | 35 | No | |||||
| Coronary heart disease | 38 | No | |||||
| Type 2 diabetes | 38 | No | |||||
| Vitamin D | 4 | No | |||||
| Dairy calcium intake | 1 | No | |||||
| Lactase persistence LCT-13910 C/T genetic variant | Northern Europeans | 1 | Hip fracture | 97,811 Danish individuals | Fixed effects meta-analysis | No | (39) |
| Height | Europeans, N = 253,288 (GIANT) | 697 | Hip fracture | 2,451 fracture cases of 417,434 individuals from UK Biobank | Two-sample (IVW) | Yes | (40) |
| Serum estradiol | Europeans Europeans |
2 | All self-reported fractures | Europeans, N = 17,650 (UK Biobank) | Two-sample (IVW) | Yes | (41) |
| 2 | Major nonvertebral osteoporotic fractures | (N = 4,379; wrist, arm, and hip) | |||||
| 2 | Wrist fractures | (N = 2,637) | |||||
| Testosterone | 3 | All self-reported fractures | (N = 17,650) | No | |||
| 3 | Major nonvertebral osteoporotic fractures | (N = 4,379; wrist, arm, and hip) | |||||
| 3 | Wrist fractures | (N = 2,637) | |||||
| Serum CRP levels | Europeans | 29 | Any fracture | 6,386 participants (59% women), of whom 1,561 sustained a fracture | One-sample | No | (42) |
| Smoking initiation | Europeans N = 1,232,091 (including UK Biobank) | 377 | Any fracture (excluding skull, face, hands and feet, pathological fractures due to malignancy, atypical femoral fractures, periprosthetic, and healed fracture) and any self-reported fractures | Europeans N = 426,795 (53,184 cases and 373,611 non-cases) (UK Biobank) | Two-sample (IVW) | Yes | (26) |
| Genetically predicted alcohol intake | Europeans N = 941,280 (including UK Biobank) | 99 | Any fracture (excluding skull, face, hands and feet, pathological fractures due to malignancy, atypical femoral fractures, periprosthetic, and healed fracture) and any self-reported fractures | Europeans N = 426,795 (53,184 cases and 373,611 non-cases) (UK Biobank) | Two-sample (IVW) | No | |
| Genetic liability to alcohol dependence | Europeans N = 46,568 (11,569 cases and 34,999 controls) | 2 | Any fracture (excluding skull, face, hands and feet, pathological fractures due to malignancy, atypical femoral fractures, periprosthetic, and healed fracture) and any self-reported fractures | Europeans N = 426,795 (53,184 cases and 373,611 non-cases) (UK Biobank) | Two-sample (IVW) | Some evidence | |
| LDL-C levels | N = 188,577 (GLSC) | 76 | Fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports | 147,200 cases and 150,085 controls (primarily of European ancestry) | Two-sample (IVW) | No | (32) |
| Gene encoding molecular target of LDL-C-lowering therapy (HMGCR) | N = 188,577 (GLSC) | 76 | Fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports | 147,200 cases and 150,085 controls (primarily of European ancestry) | No | ||
| Total serum calcium | Europeans (discovery cohort N = 39,400, replication cohort N = 21,676) | 6 | Fracture | 76,549 cases and 470,164 controls from GEFOS, EPIC-Norfolk study and UK Biobank | Two-sample (IVW) | No | (38) |
OR, Odds ratio; IVW, inverse-variance weighted; HR, hazard ratio; THS, thyroid stimulating hormone; LS, lumbar spine; FN, femoral neck.