In this manuscript we investigate the possibility of using allelic scores that index biological intermediates as a method of screening for potentially causal associations between these variables and disease. We begin first by investigating the ability of allelic scores to explain variance in modifiable exposures/biological intermediates of interest in a large population based cohort- the Avon Longitudinal Study of Parents and Children (ALSPAC). We compare the explanatory ability of allelic scores constructed from confirmed variants only, to genome-wide allelic scores generated from up to hundreds of thousands of anonymous SNPs. In order to investigate the properties of our approach, we attempt to index three biological intermediates of interest where the results of large GWAS meta-analyses are available: body mass index (BMI), C-reactive protein (CRP) and LDLc [3], [13], [14]. In order to replicate our pattern of associations, we perform the same set of analyses in an independent cohort of Australian twins (QIMR Twins) [15], [16]. We subsequently generate these allelic scores which index BMI, CRP and LDLc in publicly available data from the first Wellcome Trust Case Control Consortium [17],
