Fig. 2
From: Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference
Contrast between phenotype and genotype-based sampling strategies. Histograms show the distributions of a body mass index (BMI) and b the BMI genetic risk score (GRS) in the Avon Longitudinal Study of Parents and Children (ALSPAC). For a description of the ALSPAC data, please see Supplementary Note 2. Red bars represent the top and bottom 30% of these distributions. Mean differences in BMI, systolic blood pressure (SBP) and confounding factors (alcohol, income and education) were compared between the top and bottom 30% of the a BMI and b BMI GRS distribution. a For extreme-phenotype recall studies, participants at the extreme ends of the phenotypic distribution are invited to participate in the study. As an exemplar of this, phenotype data from 1855 individuals in ALSPAC was used. While differences in BMI and SBP are observed between the top and bottom 30% of the BMI distribution, extreme-phenotype sampling strategies are often prone to confounding and potential reverse causality (as shown by the association of the recalled strata with confounding factors). b In contrast, RbG studies have the ability to generate reliable gradients of biological difference in combination with essentially randomised groups. As an exemplar of this, genetic data from 1420 individuals in ALSPAC was used to generate a BMI GRS. Differences in BMI and SBP are observed between the top and bottom 30% of the BMI GRS distribution that are not prone to confounding and reverse causality (as shown by the lack of association of the recalled strata with confounding factors)
