Related Experiment Videos
Possible selection bias in Mendelian randomization studies: effect of body mass index on breast cancer as an example
Kezhen Fei1, Chloe A Teasdale1, Mary Beth Terry2
1Department of Epidemiology and Statistics, City University of New York (CUNY) Graduate School of Public Health and Health Policy, New York, NY, USA.
Abstract:
The inverse association of body mass index (BMI) with postmenopausal breast cancer (BC) risk observed in Mendelian Randomization (MR) studies contradicts the International Agency for Research on Cancer (IARC) classification of high BMI as a risk factor for postmenopausal BC. We investigated whether this discrepancy stems from survival-driven selection bias in the underlying GWAS. Using summary statistics from three different GWAS, higher genetically predicted BMI was inversely associated with BC risk in the BCAC consortium (odds ratio (OR): 0.74, 95% CI: 0.64, 0.84) and the UK Biobank (OR: 0.70, 95% CI: 0.56, 0.87), but showed no relationship with sibling BC (BCs) risk (OR: 1.00, 95% CI: 0.99, 1.01). These findings demonstrate that previous MR studies may suffer from selection bias driven by survivorship bias. This highlights a critical methodological vulnerability in MR studies when both exposure and outcome cause premature mortality, and the underlying population is not fully captured by current GWAS.
Related Concept Videos
Regression Toward the Mean
Randomized Experiments
Simple randomization
Simple...
Bias in Epidemiological Studies
Study Designs in Epidemiology
Observational studies are those where the researcher does not intervene but rather observes natural variations. They include cross-sectional, cohort, and case-control studies.
Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Odds Ratio