Table 1.
A selection of Mendelian randomization studies with different applications
| Application | Exposure(s) | Outcome(s) | Conclusions | References |
|---|---|---|---|---|
| Clinical | Vitamin D | Multiple sclerosis (MS) | Lower 25-hydroxyvitamin D has a causal effect on increased MS susceptibility | Mokry et al. 2015 |
| Metabolic factors | Pancreatic cancer | Causal role of body mass index (BMI) and fasting insulin in pancreatic cancer etiology | Carreras-Torres et al. 2017 | |
| C reactive protein (CRP) | Coronary heart disease (CHD) | CRP concentration is unlikely to be an important causal factor in CHD | Wensley et al. 2011 | |
| Behavioral | Cannabis use | Schizophrenia | Some evidence for a small causal effect of cannabis initiation on schizophrenia risk | Gage et al. 2017 |
| Alcohol intake | Vascular disease | Alcohol increases blood pressure and stroke risk across the distribution of intake | Chen et al. 2008; Millwood et al. 2019 | |
| Smoking heaviness | Anxiety and depression | Limited support for a causal role of smoking heaviness in depression and anxiety | Bjorngaard et al. 2013; Taylor et al. 2014 | |
| BMI and smoking | COVID-19 | Elevated BMI and smoking increase susceptibility to severe COVID-19 and sepsis | Ponsford et al. 2020 | |
| Socioeconomic | Education | Myopia | More years in education contributes to increased risk of myopia | Cuellar-Partida et al. 2016; Mountjoy et al. 2018 |
| Height and BMI | Socioeconomic position | Earlier findings suggesting that height and BMI may influence aspects of socioeconomic position may be biased by family-level dynastic effects | Tyrrell et al. 2016a; Brumpton et al. 2020 | |
| Age at menarche | Education | Positive causal effect of age at menarche on time spent in education | Gill et al. 2017 | |
| Education | Cardiovascular disease (CVD) | BMI, systolic blood pressure and smoking mediate a substantial proportion of the protective effect of education on the risk of CVD | Carter et al. 2019 | |
| Environmental | Copper and zinc | Ischemic heart disease (IHD) | Protective effect of copper and detrimental effect of zinc on IHD | Kodali et al. 2018 |
| Arsenic metabolism | Skin lesions | Evidence for a causal relationship between arsenic metabolism and skin lesion risk | Pierce et al. 2013 | |
| Malaria | Stunting | Use of genetic variation for sickle cell trait to demonstrate increased risk of stunting following malaria | Kang et al. 2013 | |
| Lifecourse | Childhood adiposity | Type 1 diabetes (T1D) | Support for an effect of childhood adiposity on T1D risk | Censin et al. 2017 |
| Age at menarche | BMI | Evidence that earlier age at menarche causes higher BMI in later life may be confounded by prepubertal BMI | Bell et al. 2018; Gill et al. 2018 | |
| Childhood body size | Coronary artery disease (CAD), type 2 diabetes (T2D), breast and prostate cancer | Whereas the causal effect of childhood body size on CAD and T2D risk is largely mediated by adulthood body size, smaller childhood body size might increase the risk of breast cancer regardless of body size in adulthood | Richardson et al. 2020b | |
| Intergenerational | Maternal BMI and glucose | Birth weight | Maternal BMI and blood glucose levels causally related to higher offspring birthweight | Tyrrell et al. 2016b |
| Maternal alcohol intake | Education | Causal adverse effect of alcohol intake during pregnancy on offspring educational attainment | Zuccolo et al. 2013 | |
| Parental education | Offspring education | Similar effect of paternal and maternal family environmental influences on offspring educational attainment | Kong et al. 2018; Wang et al. 2021a | |
| Drug targets | Niemann–Pick C1-Like 1 (NPC1L1) and HMG-CoA reductase (HMGCR) | CHD | Validation of ezetimibe and statin use for reducing risk of CHD using drug targets in NPC1L1 and HMGCR | Ference et al. 2015 |
| HMGCR | Bone mineral density (BMD) | LDL-C lowering effect of HMGCR on increased BMD suggests repurposing opportunity for statins | Li et al. 2020 | |
| HMGCR and proprotein convertase subsilisin-kexin type 9 (PCSK9) | T2D | Statins and PCSK9 inhibitors prescribed for reducing risk of CHD may increase risk of T2D | Ference et al. 2016 | |
| Angiotensin-converting enzyme (ACE) | T2D | Causal protective effect of ACE inhibitors on T2D risk | Pigeyre et al. 2020 | |
| Interleukin 6 receptor (IL-6R) | COVID-19 | Potential role of IL-6R blockage in COVID-19 severity | Bovijn et al. 2020 | |
| Molecular traits | DNA methylation | BMI | DNA methylation changes are predominantly the consequence of adiposity, rather than the cause | Wahl et al. 2017 |
| Tissue-specific gene expression | Cardiovascular traits | Identified a number of tissue-specific effects at several genomic regions on cardiovascular traits | Taylor et al. 2019 | |
| Proteins | Cardiovascular, cancer, and autoimmune outcomes | Among results was the finding of an independent role for IL18R1 and IL1RL2 on atopic dermatitis risk | Sun et al. 2018 | |
| Disease liability | Schizophrenia risk | Reproductive success | Increased genetic liability for schizophrenia does not confer a fitness advantage but does increase mating success | Lawn et al. 2019 |
| Coronary artery disease (CAD) risk | Metabolites | Genetic variants that influence CAD risk in adults are associated with large perturbations in metabolite levels in childhood | Battram et al. 2018 | |
| Atopy | Glioma | Limited evidence for an effect of atopic disease liability on risk of glioma | Disney-Hogg et al. 2018 |