Genetic Epidemiology of Complex Traits


Genetic epidemiology is a research discipline that combines genetics, molecular biology, epidemiology, statistics and bioinformatics to investigate the role of genes, the environment and their interaction in the expression of quantitative and qualitative traits and diseases in the population at large. Genetic epidemiologists often leverage population‐based family, case–control, and cohort research designs, including many with a longitudinal data collection scheme. However, characterising the influence of genes and the environment traits and diseases is complicated because most traits and diseases are influenced by a number of genetic and nongenetic factors. In addition to the problems associated with the characterisation of the genetic and environmental factors influencing traits and diseases due to the complex, multifactorial and context‐dependent pathophysiological basis of most traits and diseases, a number of issues associated with the genetic structure of human populations also complicate relevant analyses. Genetic epidemiologists attempt to deal with these issues in many ways. As the current biomedical research area era involving high‐throughput and data‐intensive assays evolves, new fields (e.g. metabolomics, epigenomics and megagenomics), technologies (e.g. high‐throughput sequencing, microarrays and mass spectrometry) and statistical approaches will be brought into genetic epidemiology, enabling more comprehensive ‘system‐level’ approaches to characterising the roles of the environment and inherited factors in disease risk, incidence, prevalence and response to therapy.

Key Concepts

  • Genetic epidemiologists investigate the role of genes, the environment and their interaction between the aetiology and population‐level incidence and prevalence of health‐related traits and diseases within families and in the population at large.
  • Factors at both the population and the individual or pathophysiological level contribute to the complexity of complex diseases, making it difficult to identify and characterise their determinants.
  • The main approaches taken by genetic epidemiologists for discovering genes influencing diseases and traits are family‐based linkage and population‐based association studies.
  • Once a variant gene has been identified, genetic epidemiologists characterise the effect of that gene on the disease burden or trait distribution in the population using a number of approaches, such as cataloguing its frequency in different populations, examining environmental factors that exacerbate or ameliorate its effects and assessing its origins and its typical effect on the time course of, for example, disease expression among individuals.
  • By integrating data from multiple high‐throughput biomedical assays (e.g. data from epigenomics, metabolomics, proteomics and metabolomics), genetic epidemiologists can apply ‘system‐level’ approaches to understand how various factors contribute to interaction in the expression of health‐related traits and diseases.

Keywords: polygenic traits; epistasis; linkage; genetic association; penetrance

Figure 1. Representation of coinheritance (i.e. genetic transmission) of a disease‐causing mutation or genetic variant and surrounding ‘founder’ chromosomal material over a number of generations. Homologous chromosomes are depicted by solid vertical lines. The numbers represent repeat lengths (alleles) associated with a microsatellite locus. The letters designate bases (alleles) at three single nucleotide polymorphic loci adjacent to the microsatellite locus. The circled ‘G’ base is a dominant and fully penetrant disease‐causing mutation. The arrows identify sites where recombination has occurred. In generation 1, two individuals produced four offspring and two that received the disease mutation (i.e. the inner two offspring). One of these offspring did not receive the entire chromosomal segment or ‘haplotype’ (123‐C–G–T) associated with the parent introducing the mutation into the population due to a recombination event that shuffled the 126 allele at the microsatellite locus with the C–G–T subhaplotype. The individuals possessing the mutation produce their own offspring and these offspring produce subsequent lines of descent (denoted by dashed lines). Two descendants of these individuals (in generation N − 1) mate with others and produce two offspring each. The two offspring from both matings receive the disease mutation, G. Note that all the diseased individuals share the basic core C–G–T haplotype, but in the first mating, the repeat allele 126 is coinherited with this haplotype, whereas the repeat allele 123 is coinherited with this haplotype in the second mating.


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Rana, Brinda K, De Vivo, Imaculata, and Schork, Nicholas J(Oct 2017) Genetic Epidemiology of Complex Traits. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005412.pub3]