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We integrated genomic structural equation modeling and multiple post\u2013genome\u2010wide association study (GWAS) methodologies to prioritize candidate SNPs associated with GD1\u2010related variation, identifying 15 loci with strong statistical support. Subsequently, diverse transcriptome\u2010wide association approaches were employed to pinpoint susceptibility gene signals strongly correlated with GD1. For selected candidate genes, we explored the potential structural consequences of missense variants using integrated structure prediction, molecular dynamics simulations, and AI\u2010based thermodynamic stability analyses. These analyses suggested that the mutations may alter protein structure and dynamics, with possible consequences for protein stability and biological function. Next, we screened a large set of publicly available traits to identify GD1\u2010related factors and biomarkers with potential relevance. Finally, a summary data\u2013based polygenic risk score (PRS) was utilized to examine risk associations between 22 autosomes and GD1. Collectively, by modeling a GD1\u2010related phenotype without direct prior measurement, this study provides an initial overview of the shared genetic architecture associated with GD1.<\/jats:p>","DOI":"10.1155\/humu\/1692822","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T10:51:42Z","timestamp":1776250302000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic Structural Equation Modeling Provides an Initial View of the Genetic Architecture Related to Type 1 Gaucher Disease"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7774-4012","authenticated-orcid":false,"given":"Shijie","family":"Ren","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2745-0159","authenticated-orcid":false,"given":"Mingmin","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8300-3327","authenticated-orcid":false,"given":"Jingyuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6458-1285","authenticated-orcid":false,"given":"Boyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7952-2594","authenticated-orcid":false,"given":"Jianping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6125-0664","authenticated-orcid":false,"given":"Xiaomeng","family":"Lang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"e_1_2_14_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.20114"},{"key":"e_1_2_14_2_2","first-page":"7","article-title":"Gaucher Disease: New Expanded Classification Emphasizing Neurological Features","volume":"13","author":"Alaei M. 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