By: Gary Taubes

In: MIT Technology Review

Date: August 28, 2018

Key Quotes:

• Epidemiology.
  • Study and analysis of the distribution, patterns and determinants of health and disease conditions in defined populations.
  • How often diseases occur in different groups of people and why.
  • Can’t always answer fundamental questions, especially related to chronic diseases.
  • Because: correlation is not causation.
  • Hard to determine which correlations are causal and which are not
• Mendelian randomization.
  • Uses innate genetic differences between people to investigate the causal relations between potentially modifiable risk factors and health outcomes in observational data.
  • Naturally occurring randomized controlled trials.
    • Genotypes are passed down randomly from parents to their offspring.
  • Risk of pleiotropy:
    • Potential that gene variants have more than one specific phenotypic effect.
  • Therefore, important that the gene variant influences only trait of interest.
    • If multiple traits are influenced => risk of confounding.
  • Example:
    • Epidemiology: high HDL is associated with lower risk of heart disease.
    • MR: however, those of us born with genes that raise our HDL do not have fewer heart attacks.
    • Conclusion: HDL may be correlated with heart disease, but HDL likely does not play a causal role.
  • Additional source:
    • Database and analytical platform for Mendelian randomization:
    • http://www.mrbase.org/