Genetic Liability to Cigarette Smoking in a Wide Range of Diseases

cigarette pack close up
Cigarette smoking has a causal role in a spectrum of diseases, but has been linked with decreased risk of prostate cancer and Parkinson’s disease.

Cigarette smoking is the unequivocal cause of a vast spectrum of diseases, yet has also been linked with a decreased risk of prostate cancer and Parkinson’s disease, according to a systematic review and meta-analysis published in eBioMedicine.

Ambiguity in the causal relationship between cigarette smoking and multiple diseases still exists, particularly outside the realm of lung diseases, coronary heart disease, and stroke. Reviewers sought to evaluate the causal association of smoking with a broad spectrum of diseases.

The investigators initiated a review and meta-analysis of 29 Mendelian randomization (MR) studies found in PubMed through mid-February 2022 concerning the genetic liability to smoking initiation or lifetime smoking in neoplasms as well as endocrine, metabolic, musculoskeletal system, nervous system, digestive system, circulatory system, and eye diseases. Researchers also conducted de novo MR analyses with data from the FinnGen study of 260,405 Finnish individuals and other genome-wide association studies.

Genetic liability to smoking initiation or lifetime smoking was significantly linked with greater risk of multiple circulatory diseases, diverticular disease, acute pancreatitis, Crohn’s disease, periodontitis, gallstone, gastroesophageal reflux, rheumatoid arthritis, osteoarthritis, epilepsy, polycystic ovarian syndrome, macular degeneration, type 2 diabetes, cancers of head, neck, pancreas, kidney, bladder, cervix, lung, esophagus, and ovaries, and myeloid leukemia. Reviewers also noted that a decrease in risk of prostate cancer and Parkinson’s disease was associated with smoking liability. Causality could not be assigned to this decrease. There was no clear evidence to associate smoking with Alzheimer’s disease or multiple sclerosis.

The review and analysis led investigators to conclude that there is “genetic evidence to support that smoking is a causal risk factor for a wide range of diseases.” Review and meta-analysis limitations include the inability to compare the magnitude of odds ratio estimates of some studies with relative risk estimates of other studies.


Larsson SC, Burgess S. Appraising the causal role of smoking in multiple diseases: A systematic review and meta-analysis of Mendelian randomization studies. EBioMedicine. Published online July 8, 2022. doi:10.1016/j.ebiom.2022.104154