RESUMEN
Despite strong transethnic genetic correlations reported in the literature for many complex traits, the non-transferability of polygenic risk scores across populations suggests the presence of population-specific components of genetic architecture. We propose an approach that models GWAS summary data for one trait in two populations to estimate genome-wide proportions of population-specific/shared causal SNPs. In simulations across various genetic architectures, we show that our approach yields approximately unbiased estimates with in-sample LD and slight upward-bias with out-of-sample LD. We analyze nine complex traits in individuals of East Asian and European ancestry, restricting to common SNPs (MAF > 5%), and find that most common causal SNPs are shared by both populations. Using the genome-wide estimates as priors in an empirical Bayes framework, we perform fine-mapping and observe that high-posterior SNPs (for both the population-specific and shared causal configurations) have highly correlated effects in East Asians and Europeans. In population-specific GWAS risk regions, we observe a 2.8× enrichment of shared high-posterior SNPs, suggesting that population-specific GWAS risk regions harbor shared causal SNPs that are undetected in the other GWASs due to differences in LD, allele frequencies, and/or sample size. Finally, we report enrichments of shared high-posterior SNPs in 53 tissue-specific functional categories and find evidence that SNP-heritability enrichments are driven largely by many low-effect common SNPs.
Asunto(s)
Etnicidad/genética , Estudio de Asociación del Genoma Completo , Herencia Multifactorial/genética , Polimorfismo de Nucleótido Simple/genética , Teorema de Bayes , Europa (Continente)/etnología , Asia Oriental/etnología , Frecuencia de los Genes , Humanos , Desequilibrio de Ligamiento , Especificidad de Órganos/genéticaRESUMEN
We report a case of Hashimoto's encephalopathy with detailed neuropsychological testing before, during and after steroid treatment, allowing a more precise characterization of the deficits and their response to treatment. It highlights that behavioral and psychotic symptoms remit before cognitive deficits and suggests that the latter may be more appropriate for guiding the duration of steroid treatment.