{"doi":"10.3390/diagnostics16010153","title":"Integrated Cross-Platform Analysis Reveals Candidate Variants and Linkage Disequilibrium-Defined Loci Associated with Osteoporosis in Korean Postmenopausal Women","abstract":"<b>Background:</b> Osteoporosis is highly prevalent in postmenopausal women, yet genome-wide association studies often miss disease-relevant variants because of incomplete single nucleotide polymorphism (SNP) coverage and platform-specific limitations. We aimed to identify genetic contributors to osteoporosis risk by integrating two exome-based genotyping platforms with multilayer analytic approaches. <b>Methods:</b> We analyzed extreme osteoporosis phenotypes in Korean postmenopausal women from the Korean Genome and Epidemiology Study (KoGES) Ansan-Anseong cohorts using the Illumina Infinium HumanExome BeadChip and the Affymetrix Axiom Exome Array. After standard quality control, single-SNP logistic regression, cross-platform overlap analysis, and three machine-learning models were applied. Predicted functional impact was evaluated using multiple in silico algorithms and conservation scores. Finally, datasets from both platforms were merged, and cross-platform linkage disequilibrium (LD) blocks were defined to identify loci containing SNPs with <i>p</i> < 1 × 10<sup>-4</sup>. <b>Results:</b> No overlapped SNP reached genome-wide significance, but rs2076212 in <i>PNPLA3</i> achieved suggestive significance (<i>p</i> < 1 × 10<sup>-5</sup>) only on the Illumina array. Cross-platform analysis identified 111 overlapping SNPs in 70 genes. Integrated machine-learning, in silico, and conservation evidence prioritized <i>ARMS2</i>, <i>CCDC92</i>, <i>NQO1</i>, <i>ZNF510</i>, <i>PTPRB</i>, and <i>DYNC2H1</i> as candidate genes. LD-block analysis revealed 10 blocks with at least one SNP at <i>p</i> < 1 × 10<sup>-4</sup>, including four chromosome 12 loci (<i>NAV2</i>, <i>BICD1</i>, <i>CCDC92</i>, <i>ZNF664</i>) that became apparent only when LD patterns were evaluated jointly across platforms. <b>Conclusions:</b> Combining dual exome arrays with LD-block analysis, machine learning, and functional prediction improved sensitivity for detecting low bone mineral density-related loci and highlighted <i>CCDC92</i>, <i>DYNC2H1</i>, <i>NQO1</i>, and related genes as biologically plausible candidates for future validation.","journal":"Diagnostics","year":2026,"id":7667,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0625,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2026-01-03","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":69249,"name":"Seoung-Jin Hong","orcid":"0000-0002-7460-8487","position":1,"is_corresponding":false},{"id":69250,"name":"Seung Il Song","orcid":"0000-0001-9504-6471","position":2,"is_corresponding":false},{"id":69251,"name":"Jeong Keun Lee","orcid":"0000-0002-5561-6297","position":3,"is_corresponding":false},{"id":69252,"name":"Gyutae Kim","orcid":null,"position":4,"is_corresponding":false},{"id":69253,"name":"Byung-Joon Choi","orcid":null,"position":5,"is_corresponding":false},{"id":69254,"name":"Suyun Seon","orcid":"0000-0002-2870-2747","position":6,"is_corresponding":false},{"id":69255,"name":"Seung Jun Kim","orcid":null,"position":7,"is_corresponding":false},{"id":69256,"name":"Ju Yeon Ban","orcid":"0000-0003-1992-5188","position":8,"is_corresponding":false},{"id":69257,"name":"Sang Wook Kang","orcid":"0000-0002-0358-2304","position":9,"is_corresponding":false},{"id":69248,"name":"Su Kang Kim","orcid":null,"position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}