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Table 1 Common bias in genetic association studies

From: Assessing the quality of published genetic association studies in meta-analyses: the quality of genetic studies (Q-Genie) tool

Bias Impact on results of genetic association study
Phenotype definition Unclear definition of phenotype or use of non-standardized definitions can lead to noise in the outcome, which compromises ability to identify corresponding susceptibility variants.
Genotyping misclassification Differential misclassification of genotypes can positively or negatively affect associations depending on the direction of misclassification. Non-differential misclassification of genotypes will bias association toward the null.
Selection of sample Source of cases and controls or participants for analysis of quantitative traits can bias the association; for example, contrasting hospital cases with controls from the general population will inflate the association.
Confounding by ethnic origin If populations from ethnic groups differ in frequency of risk alleles, confounding may occur if the populations are unevenly distributed across comparison groups.
Multiple testing Testing a multitude of genetic variants against a phenotype creates a possibility of finding significant associations by chance (type 1 error).
Relatedness Consanguinity in genetic association studies can distort the genotype-phenotype associations. Even in supposed unrelated populations, some individuals may be related. Relatedness should therefore be investigated with additional methods and adjusted for in the statistical analysis.
Treatment effects The phenotype under investigation may be modified by treatments and hence distort the size of association between genetic variants and the phenotype of interest.