Rapid developments in molecular genetics in recent years have afforded tremendous growth in our understanding of the pathophysiology of many neurologic diseases. However, progress has been slower for common diseases of major public health impact (e.g., Alzheimer's disease, essential tremor, epilepsy) than for rare Mendelian disorders (e.g., Huntington disease, neurofibromatosis). The reason for this slow progress is that in most common neurologic disorders, the genetic contributions are exceedingly complex. The research tools of genetic epidemiology are uniquely suited to deal with this type of complexity. This multidisciplinary field, which has emerged over the last 15–20 years, combines concepts and methods from epidemiology, biostatistics, clinical genetics, molecular genetics, and population genetics, as well as new approaches developed specifically for study of the genetic contributions to complex diseases.

This brief introduction to genetic epidemiology in neurologic disease will address : the basis of the complexity in the genetic contributions to common neurologic disorders, gene-environment interaction, the pathway for investigating the genetic contributions to disease risk, methods for collection of accurate information on disease occurrence in families, and research strategies commonly employed in genetic epidemiology.

Genetic epidemiologists frequently distinguish between “simple” and “complex” genetic diseases. Simple genetic diseases have inheritance patterns that conform to classical Mendelian laws, whereas complex diseases do not. Complex diseases tend to aggregate in families, but their familial distributions are inconsistent with straightforward Mendelian modes of inheritance (autosomal or X-linked, dominant or recessive). Moreover, with complex diseases both genetic and environmental factors generally contribute to susceptibility, and may interact in their influence on risk (2–4).