9 Clues 2 The Ward

Notably, genetic studies of RAN, RAS and RD were previously conducted on samples of largely European descent. This is problematic because for causal variants, differences in observed allele frequencies and linkage disequilibrium (LD) between populations could lead to associations observed in one population but not in another. Furthermore, lack of diversity in association studies leads to missed opportunities to identify novel trait loci present in certain populations, thus limiting the identification of biological clues surrounding the aetiology of a complex disorder.21 Using a single population to identify disease-associating regions constrains the ability to generalise relevant findings to other populations, and severely limits the benefits of biomedical research to only those populations with selected demographics.22 23

9 Clues 2 The Ward

Next, we brought forward all three SNPs that achieved genome-wide significance or were suggestive in both the discovery multivariate GWAS and the latent naming speed GWAS meta-analysis for replication in the CLDRC. Assessments of RAN Colours, RAN Letters, RAN Pictures and RAN Numbers were available in 318 unrelated participants. RAN Objects and RAS Letters/Numbers were not assessed in the CLDRC. Multivariate analyses of RAN Colours, RAN Letters, RAN Pictures and RAN Numbers show a significant replication of rs701825 on chromosome 10, while we observe marginal significance with rs1555839. rs6963842 on chromosome 7 does not replicate (table 2). Post-hoc univariate association analysis shows a significant replication of rs1555839 and rs701825 for RAN Letters (table 2, online supplementary table S6). The direction of effect on RAN Letters is the same for both cohorts (online supplementary table S6). 041b061a72