Table 1 Univariable drug target MR estimates for drug targets approved for indications other than lipid-lowering.

From: Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics

Drug target gene

LDL-C (OR, 95% CI)

HDL-C (OR, 95% CI)

Triglycerides (OR, 95% CI)

Mechanism of action and indication

ESR1

–

2.11 (1.13–3.93)*

–

AGONIST: Neoplasms, Hypogonadism, Menorrhagia, Primary Ovarian Insufficiency, Acne Vulgaris, Postmenopausal Osteoporosis

ANTAGONIST: Breast Neoplasms, Neoplasms

MODULATOR: Infertility, Dyspareunia, Breast Neoplasms, Postmenopausal Osteoporosis

TNF

2.03 (1.05–3.93)*

–

1.21 (0.78–1.9)

INHIBITOR: Ankylosing Spondylitis, Crohn Disease, Psoriasis, Rheumatoid Arthritis, Colitis, Ulcerative, Psoriatic Arthritis, Immune System Diseases, Juvenile Arthritis

BLK

–

–

0.46 (0.31–0.7)*

INHIBITOR: Precursor Cell Lymphoblastic Leukemia–Lymphoma, Neoplasms

DHODH

0.66 (0.44–1.0)

–

7.42 (2.32–23.71)*

INHIBITOR: Rheumatoid Arthritis, Immune System Diseases, Multiple Sclerosis

PPARG

1.67 (1.04–2.68)*

0.71 (0.35–1.48)

2.18 (1.14–4.15)*

AGONIST: Type 2 Diabetes Mellitus, Diabetes Mellitus, Ulcerative Colitis, Cardiovascular Diseases

PPARA

3.77 (1.44–9.85)*

–

–

AGONIST: Cardiovascular Diseases, Hypercholesterolemia, Dyslipidemias

NDUFA13

1.63 (1.13–2.35)*

–

1.18 (1.0–1.39)* †

INHIBITOR: Diabetes Mellitus, Type 2 Diabetes Mellitus

ALDH2

0.14 (0.07–0.29)*

–

–

INHIBITOR: Ectoparasitic Infestations, Alcoholism

NISCH

–

0.57 (0.35–0.93)*

1.16 (0.31–4.34)

AGONIST: Hypertension

ABCA1

2.05 (1.34–3.15)*

1.41 (0.66–3.0)

2.4 (1.29–4.49)*

INHIBITOR: Cardiovascular Diseases

F2

0.17 (0.05–0.59)*

0.57 (0.13–2.43)

0.35 (0.13–0.94)*

INHIBITOR: Venous Thrombosis, Thrombosis, Unstable Angina, Thrombocytopenia, Atrial Fibrillation, Embolism, Stroke

TUBB

–

7.56 (1.18–48.38)*

4.46 (2.13–9.36)*

INHIBITOR: Breast Neoplasms, Neoplasms, Hodgkin Disease, Large-Cell Anaplastic Lymphoma, Non-Small-Cell Lung Carcinoma, Gout, Familial Mediterranean Fever

VEGFA

–

0.22 (0.15–0.3)*

4.16 (2.45–7.08)* †

ANTAGONIST: Retinal Neovascularization

INHIBITOR: Diabetic Retinopathy, Retinal Neovascularization, Wet Macular Degeneration, Macular Edema, Colorectal Neoplasms, Neoplasms, Glioblastoma, Renal Cell Carcinoma, Non-Small-Cell Lung Carcinoma, Uterine Cervical Neoplasms

RAF1

2.06 (1.48– 2.86)*

–

2.63 (0.79–8.83)

INHIBITOR: Neoplasms

PSMA5

2.47 (1.8–3.39)* †

0.08 (0.02–0.29)*

–

INHIBITOR: Multiple Myeloma, Neoplasms, Mantle-Cell Lymphoma

ALOX5

–

1.74 (1.18–2.58)*

–

INHIBITOR: Asthma, Ulcerative Colitis, Rheumatoid Arthritis, Juvenile Arthritis

CACNB1

–

0.38 (0.2–0.72)*

–

BLOCKER: Cardiovascular Diseases

MODULATOR: Fibromyalgia, Seizures, Epilepsy, Neuralgia, Restless Legs Syndrome, Postherpetic Neuralgia

PLG

18.35 (5.47–61.6)*

5.48 (0.07–456.86)

0.75 (0.18–3.14)

ACTIVATOR: Thrombosis, Pulmonary Embolism, Stroke, Myocardial Infarction, Heart Failure, Hepatic Veno-Occlusive Disease

INHIBITOR: Hemorrhage, Menorrhagia

ITGB3

1.64 (1.06–2.52)*

2.79 (0.81–9.62)

–

INHIBITOR: Thrombosis, Unstable Angina

TOP1

2.3 (0.15–35.62)

–

16.72 (4.19–66.8)*

INHIBITOR: Neoplasms

  1. These drug targets showed lipid records in clinicaltrials.gov and/or the British National Formulary (BNF). OR odds ratio of CHD per 1-standard deviation increase in LDL-C, HDL-C, or triglycerides; CI confidence interval.
  2. *Indicates significance in the discovery analysis.
  3. †Indicates significance in both original and validation study and concordant direction of effect.
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