Genetic / Molecular Epidemiology

Increasingly, molecular and genetic epidemiology studies will be used to characterize risks as a result of environmental exposures and to establish overall disease causality. Exponent’s multidisciplinary team of epidemiologists, biostatisticians, toxicologists, clinicians, and environmental scientists bring together the combined expertise to address molecular epidemiology in a variety of fields, including:

  • Nutritional
  • Environmental
  • Occupational 
  • Reproductive
  • Chronic disease
  • Pharmacoepidemiology.

With the completion of the Human Genome Project and other major advances in molecular biology, molecular and genetic epidemiology has rapidly evolved in the last decade. 

Molecular and genetic epidemiology seeks to combine traditional epidemiological concepts on study design and risk measurement with principles from molecular and cellular biology, making it uniquely able to:

  • Establish disease etiology
  • Characterize disease risk factors
  • Identify susceptible populations
  • Develop targeted medicines
  • Determine strategies for disease prevention.

To address these goals, molecular and genetic epidemiology relies on the use of “biomarkers” – biological indicators of environmental exposures, internal molecular changes or effects, and/or susceptibility to disease. Genetic epidemiology in particular focuses on genetic variants as potential markers of exposure or disease risk.

Biomarkers of exposure are typically used to assess substances or their metabolites present within the body, e.g., polycyclic aromatic hydrocarbons (PAHs) from car exhaust or cigarette smoking, organophosphate pesticides and their dialkyl phosphate metabolites, or plasticizers such as phthalates or bisphenol A. Some biomarkers can be assessed in a variety of biological tissues, including urine, blood, and saliva.

Biomarkers of effect are used as indicators of a response to an exposure, e.g., decreased cholinesterase activity, the enzyme used to break down acetylcholine and allow muscle relaxation, as a result of organophosphate exposure. Biomarkers of cellular or tissue changes can also serve as indicators of preclinical disease. 

Biomarkers of susceptibility are often genetic alterations or polymorphisms leading to disease predisposition, especially in the presence of an environmental exposure. For example, carriers of the e4 allele of the APOE gene, which encodes a protein involved in cholesterol transport, have an increased likelihood of developing Alzheimer’s disease. 

Early on, molecular and genetic epidemiology was largely hypothesis-driven, with assays designed to examine effects of specific exposures on a priori chosen biomarkers. Typical assays included studies on chromosome aberration, micronuclei formations, and the comet assay to measure DNA strand breaks. However, recent molecular biology advances have shifted research towards hypothesis-free, discovery-focused approaches. Genome-wide association studies are able to screen millions of genetic polymorphisms for possible associations with an exposure or disease. Building on the overall complexity of disease etiology, platforms to measure the epigenome (e.g., DNA methylation), proteome, and metabolome have become available and progressively used in the scientific community. With the advent of these novel “omics” technologies come important methodological issues of multiple hypothesis testing, reproducibility, and large data management.