RESUMO
Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10-8). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10-4). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10-11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.
Assuntos
Esclerose Lateral Amiotrófica/genética , Coenzima A Ligases/genética , Genes/genética , Predisposição Genética para Doença/genética , Esclerose Lateral Amiotrófica/etnologia , Povo Asiático/genética , Estudos de Casos e Controles , China , Coenzima A Ligases/fisiologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Japão , Masculino , Polimorfismo de Nucleotídeo Único/genética , População Branca/genéticaRESUMO
In appropriate situations, large populations of geese exhibit dynamical rearrangements by repeated mergers and splits among the groups. We describe the grouping process in terms of a mean-field model based on the Smoluchowski equation of coagulation with fragmentation and observationally plausible kernels. To verify our model, we conducted field observations on skeins of airborne geese, noting both the group-size distribution and the group-forming processes. We found that the group-size distribution we obtained in our field measurements could be represented by a fractional power function with an exponential cutoff. This function matches the asymptotic form of the steady-state solution of our model. Furthermore, we estimated the effective number of individuals involved in interactions by comparison of the model to our field data.
