Population-based family studies in genetic epidemiology
Hopper, J.L.; Bishop, D.T.; Easton, D.F.
Lancet 366(9494): 1397-1406
2005
ISSN/ISBN: 1474-547X PMID: 16226618 DOI: 10.1016/s0140-6736(05)67570-8Document Number: 257356
Designs that involve families (the traditional strength of genetic epidemiology) and population-based sampling (the traditional strength of environmental epidemiology) allow investigation of both genes and environment, separately or together, and allow valid inference to the population. These case-control-family designs (including those involving twin pairs), can be regarded as retrospective cohort studies of relatives, and can be used for: determining familial risks and genetic models; estimating risk (penetrance) for measured genotypes; genetic association studies; stratifying risks by family history and known mutation status; and studying modifiers of risk in genetically susceptible individuals. Follow-up of families allows genetic and environmental risks to be studied prospectively. We discuss statistical methods, theoretical and practical strengths, limitations, and other issues. Given their versatility, population-based family studies could become a principal framework in epidemiology, and move genetics from its traditional focus on high-risk families to give it a wider clinical and population health relevance.