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Gene-Environment Interaction Analysis and Causal Inference on ADRD and Cognitive Decline

Gene-Environment Interaction Analysis and Causal Inference on ADRD and Cognitive Decline

Principal Investigator: Dr Li-San Wang
Approved Research ID: 50806
Approval date: March 4th 2020

Lay summary

Genome-wide association studies have documented the relationship between specific gene and Alzheimer's disease. In this study, we are interested in further exploring whether environmental shocks play a critical role in developing Alzheimer's disease and related dementias (ADRD) and cognitive impairment for people whose genotype are associated with it. We will analyse UK Biobank data and explore various natural experiments to identify causal relationships between possible gene-environment interactions and dementia.

As a first example, we use an event of air pollution disaster as a natural experiment to study whether early-life living environmental conditions are driving factors in developing ADRD and cognitive impairment. The research design is based on the Great Smog of London in December 1952 (also known as "killer smog"). Using this event as a natural experiment, we are able to study the causal effect of the extreme air pollution on human's health, and further leverage the abundant information on individual genes to examine whether heterogeneity of treatment effects can be attributed to genetic endowment. We will exploit the variation in the region of birth, timing of birth, and individual genotype to estimate the treatment effect of air pollution on ADRD-risk carriers. The UK Biobank provides an excellent data set as it recruited a large cohort of elderly who were born around 1952 and collected individual genetic variants.

This study aims to be a contribution to gene-environment interaction analysis, allowing us to understand the development of ADRD better. As the worldwide population is aging, identifying the causal effect of living environmental shocks on such mental disorders is of interest since specific policy interventions can be designed to improve one's life.