Atlas Khan, Gul Karakoc, Ge Liu, Jacy Zanussi, Nancy J Olsen, Mingjian Shi, Nancy J Cox, Jonathan Mosley, Charles Michael Stein, Krysztof Kiryluk, Wei-Qi Wei, Frank Mentch, Scott Hebbring, James Linneman, Vivian Kawai
{"title":"在没有自身免疫性疾病的情况下，系统性红斑狼疮与抗核抗体试验阳性之间的遗传关系。","authors":"Atlas Khan, Gul Karakoc, Ge Liu, Jacy Zanussi, Nancy J Olsen, Mingjian Shi, Nancy J Cox, Jonathan Mosley, Charles Michael Stein, Krysztof Kiryluk, Wei-Qi Wei, Frank Mentch, Scott Hebbring, James Linneman, Vivian Kawai","doi":"10.1136/lupus-2024-001476","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>We defined the genetic factors associated with a positive ANA test (ANA+) in the absence of autoimmune disease and tested the association with SLE.</p><p><strong>Methods: </strong>Using a case-control design, we performed a genome-wide association study (GWAS) in individuals of European ancestry without an autoimmune disease who had ANA tested as part of clinical care from DNA biobanks linked to de-identified electronic medical records: BioVU and Electronic Medical Records and Genomics. GWAS results were meta-analysed and single nucleotide polymorphism (SNP) heritability was calculated. A polygenic risk score (PRS) for ANA+ and for SLE was constructed and compared in patients with SLE, ANA+ and ANA negative (ANA-) individuals without autoimmune disease and general controls who never had ANA testing performed.</p><p><strong>Results: </strong>A total of 7287 individuals of European ancestry were included in the meta-analyses (2169 ANA+ and 5118 ANA-); an SNP upstream of the <i>TSBP1</i> in the HLA locus (rs1967688) was associated with ANA+ (p=4.84×10<sup>-8</sup>). SNP heritability for ANA+ was low (h<sup>2</sup> <sub>SNP</sub>= 0.04), and the PRS for ANA+ was not significantly different in ANA+ and ANA- individuals. In contrast, the PRS for SLE was significantly higher in SLE compared with ANA+ individuals (p<2.2×10<sup>-16</sup>) but did not differ among ANA+, ANA- and general control groups (p=0.17).</p><p><strong>Conclusions: </strong>ANA+ occurring in the absence of autoimmune disease has a genetic association with the <i>HLA</i> region, but overall heritability is low. In addition, few SLE-associated SNPs were associated with ANA+, and the PRS for SLE was not associated with ANA+, indicating limited genetic overlap.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164615/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genetic relationships between systemic lupus erythematosus and a positive antinuclear antibody test in the absence of autoimmune disease.\",\"authors\":\"Atlas Khan, Gul Karakoc, Ge Liu, Jacy Zanussi, Nancy J Olsen, Mingjian Shi, Nancy J Cox, Jonathan Mosley, Charles Michael Stein, Krysztof Kiryluk, Wei-Qi Wei, Frank Mentch, Scott Hebbring, James Linneman, Vivian Kawai\",\"doi\":\"10.1136/lupus-2024-001476\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>We defined the genetic factors associated with a positive ANA test (ANA+) in the absence of autoimmune disease and tested the association with SLE.</p><p><strong>Methods: </strong>Using a case-control design, we performed a genome-wide association study (GWAS) in individuals of European ancestry without an autoimmune disease who had ANA tested as part of clinical care from DNA biobanks linked to de-identified electronic medical records: BioVU and Electronic Medical Records and Genomics. GWAS results were meta-analysed and single nucleotide polymorphism (SNP) heritability was calculated. A polygenic risk score (PRS) for ANA+ and for SLE was constructed and compared in patients with SLE, ANA+ and ANA negative (ANA-) individuals without autoimmune disease and general controls who never had ANA testing performed.</p><p><strong>Results: </strong>A total of 7287 individuals of European ancestry were included in the meta-analyses (2169 ANA+ and 5118 ANA-); an SNP upstream of the <i>TSBP1</i> in the HLA locus (rs1967688) was associated with ANA+ (p=4.84×10<sup>-8</sup>). SNP heritability for ANA+ was low (h<sup>2</sup> <sub>SNP</sub>= 0.04), and the PRS for ANA+ was not significantly different in ANA+ and ANA- individuals. In contrast, the PRS for SLE was significantly higher in SLE compared with ANA+ individuals (p<2.2×10<sup>-16</sup>) but did not differ among ANA+, ANA- and general control groups (p=0.17).</p><p><strong>Conclusions: </strong>ANA+ occurring in the absence of autoimmune disease has a genetic association with the <i>HLA</i> region, but overall heritability is low. In addition, few SLE-associated SNPs were associated with ANA+, and the PRS for SLE was not associated with ANA+, indicating limited genetic overlap.</p>\",\"PeriodicalId\":18126,\"journal\":{\"name\":\"Lupus Science & Medicine\",\"volume\":\"12 1\",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-06-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164615/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lupus Science & Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/lupus-2024-001476\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lupus Science & Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/lupus-2024-001476","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
Genetic relationships between systemic lupus erythematosus and a positive antinuclear antibody test in the absence of autoimmune disease.
Objective: We defined the genetic factors associated with a positive ANA test (ANA+) in the absence of autoimmune disease and tested the association with SLE.
Methods: Using a case-control design, we performed a genome-wide association study (GWAS) in individuals of European ancestry without an autoimmune disease who had ANA tested as part of clinical care from DNA biobanks linked to de-identified electronic medical records: BioVU and Electronic Medical Records and Genomics. GWAS results were meta-analysed and single nucleotide polymorphism (SNP) heritability was calculated. A polygenic risk score (PRS) for ANA+ and for SLE was constructed and compared in patients with SLE, ANA+ and ANA negative (ANA-) individuals without autoimmune disease and general controls who never had ANA testing performed.
Results: A total of 7287 individuals of European ancestry were included in the meta-analyses (2169 ANA+ and 5118 ANA-); an SNP upstream of the TSBP1 in the HLA locus (rs1967688) was associated with ANA+ (p=4.84×10-8). SNP heritability for ANA+ was low (h2SNP= 0.04), and the PRS for ANA+ was not significantly different in ANA+ and ANA- individuals. In contrast, the PRS for SLE was significantly higher in SLE compared with ANA+ individuals (p<2.2×10-16) but did not differ among ANA+, ANA- and general control groups (p=0.17).
Conclusions: ANA+ occurring in the absence of autoimmune disease has a genetic association with the HLA region, but overall heritability is low. In addition, few SLE-associated SNPs were associated with ANA+, and the PRS for SLE was not associated with ANA+, indicating limited genetic overlap.
期刊介绍：
Lupus Science & Medicine is a global, peer reviewed, open access online journal that provides a central point for publication of basic, clinical, translational, and epidemiological studies of all aspects of lupus and related diseases. It is the first lupus-specific open access journal in the world and was developed in response to the need for a barrier-free forum for publication of groundbreaking studies in lupus. The journal publishes research on lupus from fields including, but not limited to: rheumatology, dermatology, nephrology, immunology, pediatrics, cardiology, hepatology, pulmonology, obstetrics and gynecology, and psychiatry.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
