Clinical trait-specific genetic analysis in Behçet's disease identifies novel loci associated with ocular and neurological involvement
Behçet's disease is a complex inflammatory vasculitis with a broad spectrum of clinical manifestations. The purpose of this study was to investigate the genetics underlying specific clinical features of Behçet's disease. A total of 436 patients with Behçet's disease from Turkey were s...
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| Veröffentlicht in: | Clinical immunology (Orlando, Fla.) Fla.), 2023-08, Vol.253, p.109657-109657, Article 109657 |
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| creator | Casares-Marfil, Desiré Esencan, Deren Alibaz-Oner, Fatma Çefle, Ayşe Yazıcı, Ayten Duzgun, Nursen Aşık, Mehmet Ali Özbek, Süleyman Cinar, Muhammet Alpsoy, Erkan Bilge, Sule Yasar Kasifoglu, Timucin Saruhan-Direskeneli, Guher Direskeneli, Haner Sawalha, Amr H. |
| description | Behçet's disease is a complex inflammatory vasculitis with a broad spectrum of clinical manifestations. The purpose of this study was to investigate the genetics underlying specific clinical features of Behçet's disease. A total of 436 patients with Behçet's disease from Turkey were studied. Genotyping was performed using the Infinium ImmunoArray-24 BeadChip. After imputation and quality control measures, logistic regressions adjusting for sex and the first five principal components were performed for each clinical trait using a case-case genetic analysis approach. A weighted genetic risk score was calculated for each clinical feature. Genetic association analyses of previously identified susceptibility loci in Behçet's disease revealed a genetic association between ocular lesions and HLA-B/MICA (rs116799036: OR = 1.85 [95% CI = 1.35–2.52], p-value = 1.1 × 10−4). The genetic risk score was significantly higher in Behçet's disease patients with ocular lesions compared to those without ocular involvement, which is explained by the genetic variation in the HLA region. New genetic loci predisposing to specific clinical features in Behçet's disease were suggested when genome-wide variants were evaluated. The most significant associations were observed in ocular involvement with SLCO4A1 (rs6062789: OR = 0.41 [95% CI = 0.30–0.58], p-value = 1.92 × 10−7), and neurological involvement with DDX60L (rs62334264: OR = 4.12 [95% CI 2.34 to 7.24], p-value = 8.85 × 10−7). Our results emphasize the role of genetic factors in predisposing to specific clinical manifestations in Behçet's disease, and might shed additional light into disease heterogeneity, pathogenesis, and variability of Behçet's disease presentation across populations.
•Genetic contributions to clinical manifestations in Behçet's disease were comprehensively evaluated.•HLA-B/MICA locus predisposes to ocular involvement in Behçet's disease (odds ratio ∼ 2)•SLCO4A (odds ratio ∼ 2) and DDX60L (odds ratio ∼ 4) predispose to ocular and neurological involvement in Behçet's disease, respectively.•Genetics play a role in disease heterogeneity in Behçet's disease. |
| doi_str_mv | 10.1016/j.clim.2023.109657 |
| format | Article |
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•Genetic contributions to clinical manifestations in Behçet's disease were comprehensively evaluated.•HLA-B/MICA locus predisposes to ocular involvement in Behçet's disease (odds ratio ∼ 2)•SLCO4A (odds ratio ∼ 2) and DDX60L (odds ratio ∼ 4) predispose to ocular and neurological involvement in Behçet's disease, respectively.•Genetics play a role in disease heterogeneity in Behçet's disease.</description><identifier>ISSN: 1521-6616</identifier><identifier>ISSN: 1521-7035</identifier><identifier>EISSN: 1521-7035</identifier><identifier>DOI: 10.1016/j.clim.2023.109657</identifier><identifier>PMID: 37271218</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Behcet Syndrome - complications ; Behcet Syndrome - genetics ; Behçet's disease ; Clinical manifestations ; Disease Susceptibility - complications ; Face ; Genetics ; HLA ; Humans ; MHC ; Ocular lesions ; Phenotype ; Vasculitis - complications</subject><ispartof>Clinical immunology (Orlando, Fla.), 2023-08, Vol.253, p.109657-109657, Article 109657</ispartof><rights>2023 Elsevier Inc.</rights><rights>Copyright © 2023 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-16bc4eda25490ce93335697ab17d39c0a6866b894ba2242fc7108e89934a40933</citedby><cites>FETCH-LOGICAL-c456t-16bc4eda25490ce93335697ab17d39c0a6866b894ba2242fc7108e89934a40933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1521661623004205$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37271218$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Casares-Marfil, Desiré</creatorcontrib><creatorcontrib>Esencan, Deren</creatorcontrib><creatorcontrib>Alibaz-Oner, Fatma</creatorcontrib><creatorcontrib>Çefle, Ayşe</creatorcontrib><creatorcontrib>Yazıcı, Ayten</creatorcontrib><creatorcontrib>Duzgun, Nursen</creatorcontrib><creatorcontrib>Aşık, Mehmet Ali</creatorcontrib><creatorcontrib>Özbek, Süleyman</creatorcontrib><creatorcontrib>Cinar, Muhammet</creatorcontrib><creatorcontrib>Alpsoy, Erkan</creatorcontrib><creatorcontrib>Bilge, Sule Yasar</creatorcontrib><creatorcontrib>Kasifoglu, Timucin</creatorcontrib><creatorcontrib>Saruhan-Direskeneli, Guher</creatorcontrib><creatorcontrib>Direskeneli, Haner</creatorcontrib><creatorcontrib>Sawalha, Amr H.</creatorcontrib><title>Clinical trait-specific genetic analysis in Behçet's disease identifies novel loci associated with ocular and neurological involvement</title><title>Clinical immunology (Orlando, Fla.)</title><addtitle>Clin Immunol</addtitle><description>Behçet's disease is a complex inflammatory vasculitis with a broad spectrum of clinical manifestations. The purpose of this study was to investigate the genetics underlying specific clinical features of Behçet's disease. A total of 436 patients with Behçet's disease from Turkey were studied. Genotyping was performed using the Infinium ImmunoArray-24 BeadChip. After imputation and quality control measures, logistic regressions adjusting for sex and the first five principal components were performed for each clinical trait using a case-case genetic analysis approach. A weighted genetic risk score was calculated for each clinical feature. Genetic association analyses of previously identified susceptibility loci in Behçet's disease revealed a genetic association between ocular lesions and HLA-B/MICA (rs116799036: OR = 1.85 [95% CI = 1.35–2.52], p-value = 1.1 × 10−4). The genetic risk score was significantly higher in Behçet's disease patients with ocular lesions compared to those without ocular involvement, which is explained by the genetic variation in the HLA region. New genetic loci predisposing to specific clinical features in Behçet's disease were suggested when genome-wide variants were evaluated. The most significant associations were observed in ocular involvement with SLCO4A1 (rs6062789: OR = 0.41 [95% CI = 0.30–0.58], p-value = 1.92 × 10−7), and neurological involvement with DDX60L (rs62334264: OR = 4.12 [95% CI 2.34 to 7.24], p-value = 8.85 × 10−7). Our results emphasize the role of genetic factors in predisposing to specific clinical manifestations in Behçet's disease, and might shed additional light into disease heterogeneity, pathogenesis, and variability of Behçet's disease presentation across populations.
•Genetic contributions to clinical manifestations in Behçet's disease were comprehensively evaluated.•HLA-B/MICA locus predisposes to ocular involvement in Behçet's disease (odds ratio ∼ 2)•SLCO4A (odds ratio ∼ 2) and DDX60L (odds ratio ∼ 4) predispose to ocular and neurological involvement in Behçet's disease, respectively.•Genetics play a role in disease heterogeneity in Behçet's disease.</description><subject>Behcet Syndrome - complications</subject><subject>Behcet Syndrome - genetics</subject><subject>Behçet's disease</subject><subject>Clinical manifestations</subject><subject>Disease Susceptibility - complications</subject><subject>Face</subject><subject>Genetics</subject><subject>HLA</subject><subject>Humans</subject><subject>MHC</subject><subject>Ocular lesions</subject><subject>Phenotype</subject><subject>Vasculitis - complications</subject><issn>1521-6616</issn><issn>1521-7035</issn><issn>1521-7035</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2O0zAUhSMEYoaBF2CBvINNiu0kTiwhoaHiTxqJDawtx75tb-XYxXaC5gl4FB6EF8OlZQQbVseyz_2OdU9VPWV0xSgTL_cr43BaccqbciFF19-rLlnHWd3Tprt_PgvBxEX1KKU9pbTjXDysLpqe94yz4bL6vnbo0WhHctSY63QAgxs0ZAseclHttbtNmAh68gZ2P39Afp6IxQQ6AUELPhc_JOLDAo64YJDolIroDJZ8w7wjwcxOx4KyxMMcgwvb35Hol-AWmArjcfVgo12CJ2e9qr68e_t5_aG--fT-4_r6pjZtJ3LNxGhasJp3raQGZNM0nZC9HllvG2moFoMQ4yDbUXPe8o3pGR1gkLJpdUuL_ap6feIe5nECa0p01E4dIk463qqgUf374nGntmFRrOxOth0thBdnQgxfZ0hZTZgMOKc9hDkpPnDeU8n5MYyfrCaGlCJs7nIYVccK1V4dK1THCtWpwjL07O8f3o386awYXp0MUPa0IESVDII3YDGCycoG_B__Fw6ysOc</recordid><startdate>20230801</startdate><enddate>20230801</enddate><creator>Casares-Marfil, Desiré</creator><creator>Esencan, Deren</creator><creator>Alibaz-Oner, Fatma</creator><creator>Çefle, Ayşe</creator><creator>Yazıcı, Ayten</creator><creator>Duzgun, Nursen</creator><creator>Aşık, Mehmet Ali</creator><creator>Özbek, Süleyman</creator><creator>Cinar, Muhammet</creator><creator>Alpsoy, Erkan</creator><creator>Bilge, Sule Yasar</creator><creator>Kasifoglu, Timucin</creator><creator>Saruhan-Direskeneli, Guher</creator><creator>Direskeneli, Haner</creator><creator>Sawalha, Amr H.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20230801</creationdate><title>Clinical trait-specific genetic analysis in Behçet's disease identifies novel loci associated with ocular and neurological involvement</title><author>Casares-Marfil, Desiré ; 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The purpose of this study was to investigate the genetics underlying specific clinical features of Behçet's disease. A total of 436 patients with Behçet's disease from Turkey were studied. Genotyping was performed using the Infinium ImmunoArray-24 BeadChip. After imputation and quality control measures, logistic regressions adjusting for sex and the first five principal components were performed for each clinical trait using a case-case genetic analysis approach. A weighted genetic risk score was calculated for each clinical feature. Genetic association analyses of previously identified susceptibility loci in Behçet's disease revealed a genetic association between ocular lesions and HLA-B/MICA (rs116799036: OR = 1.85 [95% CI = 1.35–2.52], p-value = 1.1 × 10−4). The genetic risk score was significantly higher in Behçet's disease patients with ocular lesions compared to those without ocular involvement, which is explained by the genetic variation in the HLA region. New genetic loci predisposing to specific clinical features in Behçet's disease were suggested when genome-wide variants were evaluated. The most significant associations were observed in ocular involvement with SLCO4A1 (rs6062789: OR = 0.41 [95% CI = 0.30–0.58], p-value = 1.92 × 10−7), and neurological involvement with DDX60L (rs62334264: OR = 4.12 [95% CI 2.34 to 7.24], p-value = 8.85 × 10−7). Our results emphasize the role of genetic factors in predisposing to specific clinical manifestations in Behçet's disease, and might shed additional light into disease heterogeneity, pathogenesis, and variability of Behçet's disease presentation across populations.
•Genetic contributions to clinical manifestations in Behçet's disease were comprehensively evaluated.•HLA-B/MICA locus predisposes to ocular involvement in Behçet's disease (odds ratio ∼ 2)•SLCO4A (odds ratio ∼ 2) and DDX60L (odds ratio ∼ 4) predispose to ocular and neurological involvement in Behçet's disease, respectively.•Genetics play a role in disease heterogeneity in Behçet's disease.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>37271218</pmid><doi>10.1016/j.clim.2023.109657</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Behcet Syndrome - complications Behcet Syndrome - genetics Behçet's disease Clinical manifestations Disease Susceptibility - complications Face Genetics HLA Humans MHC Ocular lesions Phenotype Vasculitis - complications |
| title | Clinical trait-specific genetic analysis in Behçet's disease identifies novel loci associated with ocular and neurological involvement |
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