Study Designs in Genetic Epidemiology

Table 2

Main study designs in genetic epidemiology.

Research question/problem	Type of study	Unit of study	Type of measurement	Aim
Is there evidence of phenotypic aggregation within families?	Familial aggregation	Case-parent; Case-parent-grandparent	Recurrence risk ratio; Correlation; Odds ratio; Conditional regression logistic	Identifying new disease genes
Is the pattern of aggregation reliable with an effect of genes?	Heritability	Twin study	Variance component heritability	Identifying new disease genes
Is there evidence of a gene with subnational enough effects to justify expensive studies?	Segregation	Familial pedigree	Maximum likelihood estimation; Binomial distribution	Identifying new disease genes
Where in the genome is a causative gene most likely to lie?	Linkage	Case; disease of interest and control group; disease-free	Parametric: maximum likelihood; Nonparametric: mean, proportion, chi square, likelihood test	Identifying new disease genes
Is there a causative polymorphism?	Association; Linkage disequilibrium; Cohort; Case only study	Related—case control; Unrelated-case control; Exposure and non-exposure group; Case groups	Transmission disequilibrium test; Chi square independence; Odds ratio; Conditional regression logistic Correlation; Lewontine’s D prime; Relative risk, Attributable risk; Exposure odds ratio estimate	Characterizing known disease genes
Estimate allele frequency	Cross-sectional		Prevalence; Correlation	Characterizing known disease genes
Estimating penetrance	Association; Cohort	Related—case control; Familial cohort	Odds ratio; Conditional regression logistic; Risk ratio; Attributable risk	Characterizing known disease genes
Evaluating strategies for prevention of genetic diseases	Experimental; Retrospective cohort	Clinical trial (intervention and control group); Exposure and non-exposure groups	Risk ratio; Attributable risk; Risk ratio; Attributable risk	Characterizing known disease genes