Comparative Insular Population Genetics of Gaucher Disease (GBA1): Edo-Period Sakoku Genetic Drift and Neuronopathic Predominance in Japan Versus Viking Maritime Gene Flow, Monastic Abductions, and Allelic Admixture in the British Isles

Insular populations provide natural laboratories for observing how geopolitical boundary conditions, sex-biased maritime migrations, and cultural isolation shape the allelic architecture of Mendelian disorders. This monograph presents a comparative population-genetic, epidemiological, and biophysical analysis of Gaucher disease (OMIM #230800, #230900, #231000)—an autosomal recessive lysosomal storage disorder caused by biallelic pathogenic variants in the beta-glucocerebrosidase gene (GBA1 on chromosome 1q21)—across two major Eurasian island nations: Japan and the United Kingdom. In Japan, over two centuries of Tokugawa-era maritime isolation (Sakoku [鎖国], 1639–1854) and internal feudal domain (Han [藩]) partitioning prevented West Eurasian gene flow and amplified local genetic drift across isolated demes, yielding a low birth prevalence of ~1 in 330,000 live births (~150–211 diagnosed patients nationwide), complete absence of the neuroprotective N370S allele, and high concentration of severe destabilizing variants—L444P (43.6%) and F213I (14.9%)—resulting in 55%–60% of Japanese patients presenting with acute (Type 2) or subacute (Type 3) neuronopathic disease. Conversely, the British Isles functioned during the Viking Age (793–1066 CE) as an open maritime nexus characterized by sex-asymmetric admixture, including the documented abduction of British and Irish women and monastics into Norse settlements alongside extensive European gene flow. This regime maintained broad autosomal heterozygosity in the UK (~300–350 diagnosed patients; birth incidence ~1 in 60,000), blending N370S alleles (~90%–94% Type 1 non-neuronopathic phenotype via compound heterozygote rescue) with Scandinavian L444P lineages. Finally, we formulate a deterministic zero-knowledge genomic registry architecture over the 64-bit Goldilocks prime field F_p (p = 2^64 - 2^32 + 1) integrating QFS-zkVM, RTO P2.0, Q-SAFA, PHOENIX_BRIDGE, and Human-in-Command (HIC) governance under the Strict No-Learn Covenant (NLL-v1.0-2026)