Genetic Architecture of Rheumatoid Arthritis in African-Americans

非裔美国人类风湿关节炎的遗传结构

• 批准号: 9067316
• 负责人: Maria Ioana Danila
• 金额: $ 13.9万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9067316
• 关键词: African American; Alleles; Ankylosing spondylitis; Architecture; Arthritis; Asians; Autoantibodies; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Bioinformatics; CCR6 gene; CTLA4 gene; Candidate Disease Gene; Caucasians; Celiac Disease; Chronic; Clinical; Clinical Data; Clinical Research; Collaborations; Complex; Custom; Data; Data Set; Development; Development Plans; Diagnostic; Disease; Disease susceptibility; Environmental Risk Factor; Epidemiology; Epitopes; Etiology; European; Evaluation; Funding; Genetic; Genetic Determinism; Genetic Markers; Genetic Polymorphism; Genetic Risk; Genotype; Goals; HLA-DRB1; Heterogeneity; Individual; Inflammatory Bowel Diseases; Insulin-Dependent Diabetes Mellitus; Knowledge; Letters; Lupus; Maps; Master of Science; Medical Genetics; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Minority Groups; Odds Ratio; Outcome; PTPN22 gene; Participant; Pathogenesis; Patients; Peptide antibodies; Play; Population; Population Group; Positioning Attribute; Predisposition; Premature Mortality; Process; Psoriasis; Public Health; Reporting; Research; Research Personnel; Rest; Rheumatism; Rheumatoid Arthritis; Rheumatoid Factor; Rheumatology; Risk; Role; Serological; Serum; Severities; Severity of illness; Single Nucleotide Polymorphism; Techniques; Testing; Therapeutic; Training; Twin Studies; United States National Institutes of Health; arthritis registry; autoimmune thyroid disease; base; career; career development; clinically relevant; cohort; cyclic citrullinated peptide; disability; disease phenotype; ethnic difference; genetic analysis; genetic association; genome wide association study; genomic data; health care delivery; high risk; improved; joint destruction; meetings; point of care; population based; predictive marker; predictive modeling; racial and ethnic; risk variant; socioeconomics

DESCRIPTION (provided by applicant): The applicant's career goal is to become an independently funded investigator in the genetics of rheumatic diseases, particularly rheumatoid arthritis (RA). To meet this goal, the applicant proposes a career development plan with emphasis on didactic training in the principles of epidemiology and statistical genetics methods by pursing courses towards a Masters of Science in Public Health in Clinical Research. In addition, she will obtain hands-on training in bioinformatics. She will become well versed in using state-of-the-art statistical techniques that can accommodate the unique challenges posed by large genetic data sets. The candidate has assembled a strong interdisciplinary mentoring team with proven track record of successful mentorship and academic accomplishment in rheumatology, epidemiology and statistical genetics. The research component of this mentored patient-oriented research career development award proposes to identify genetic associations with risk and severity of RA in African Americans and to build predictive models for RA risk and outcome using clinical and genomic data. Data from ~ 1000 African Americans RA participants and ~1700 African American controls is available from the NIH-funded Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR) Registry and from local and national collaborations. Genotyping data will be available from the ImmunoChip, a custom array of ~200,000 rare and common single nucleotide polymorphisms (SNPs) developed by the ImmunoChip Consortium. The ImmunoChip contains SNPs selected from the most strongly associated makers discovered in Caucasian and Asian populations through GWAS strategy in autoimmune diseases including RA, type 1 diabetes, lupus, celiac disease, autoimmune thyroid disease, inflammatory bowel disease, ankylosing spondylitis, psoriasis and other diseases. Genotyping is currently underway (see letter from Dr. Peter Gregersen) using institutional funds from UAB provided by Dr. Lou Bridges and will be available by the requested start date of this K23 application. The scientific aims of the study are: 1) to determine whether genetic markers of autoimmunity validated in European and Asian populations influence the risk of developing RA in African Americans; 2) to determine whether the genetic markers of susceptibility to RA play a role in radiographic severity of RA in African Americans; 3) to develop and test predictive models for RA risk and outcome using clinical and genetic data in African Americans. This project will greatly improve our understanding of the genetic influences on the RA risk and outcome and will provide essential training for Dr. Danila' development as an independent investigator.

描述（由申请人提供）：申请人的职业目标是成为一个独立资助的风湿性疾病，特别是类风湿性关节炎（RA）的遗传学研究者。为了实现这一目标，申请人提出了一个职业发展计划，重点是通过追求公共卫生临床研究硕士课程，在流行病学和统计遗传学方法的原则教学培训。此外，她还将获得生物信息学方面的实践培训。她将精通使用最先进的统计技术，可以适应大型遗传数据集带来的独特挑战。候选人组建了一支强大的跨学科指导团队，在风湿病学，流行病学和统计遗传学方面具有成功的指导和学术成就的良好记录。该指导性的以患者为导向的研究职业发展奖的研究部分建议确定非裔美国人RA风险和严重程度的遗传相关性，并使用临床和基因组数据建立RA风险和结果的预测模型。来自约1000名非裔美国人RA参与者和约1700名非裔美国人对照的数据可从NIH资助的非裔美国人RA纵向评估联盟（CLEAR）登记处以及地方和国家合作中获得。基因分型数据将从免疫芯片中获得，免疫芯片是由免疫芯片联盟开发的约200，000种罕见和常见单核苷酸多态性（SNP）的定制阵列。免疫芯片包含从通过GWAS策略在包括RA、1型糖尿病、狼疮、乳糜泻、自身免疫性甲状腺疾病、炎症性肠病、强直性脊柱炎、银屑病和其他疾病在内的自身免疫性疾病中发现的高加索和亚洲人群中最强相关的标记中选择的SNP。基因分型目前正在进行中（见Peter Gregersen博士的信），使用的是Lou Bridges博士提供的UAB机构资金，并将在本K23申请的要求开始日期之前提供。本研究的科学目的是：1）确定在欧洲和亚洲人群中验证的自身免疫遗传标记是否影响非洲裔美国人发生RA的风险; 2）确定RA易感性遗传标记是否在非洲裔美国人RA的放射学严重程度中发挥作用; 3）使用非裔美国人的临床和遗传数据开发和测试RA风险和结果的预测模型。该项目将大大提高我们对遗传因素对RA风险和结局的影响的理解，并将为Danila博士作为独立研究者的发展提供必要的培训。

项目成果

The evolution of histopathologic findings in adult Still disease.

成人斯蒂尔病组织病理学结果的演变。

• DOI: 10.1097/dad.0b013e31820c6dd1
• 发表时间: 2011
• 期刊: The American Journal of dermatopathology
• 作者: Woods,MatthewT;Gavino,ACarlo;Burford,HollyN;Hughey,SLauren;Mercado,Patricia;Danila,Maria;Andea,AleodorA
• 通讯作者: Andea,AleodorA

Use of path modeling to inform a clinical decision support application to encourage osteoporosis medication use.

• DOI: 10.1016/j.sapharm.2020.09.010
• 发表时间: 2021-07
• 期刊: RESEARCH IN SOCIAL & ADMINISTRATIVE PHARMACY
• 影响因子: 3.9
• 作者: Miller, Michael J.;Jou, Tzuchen;Danila, Maria, I;Mudano, Amy S.;Rahn, Elizabeth J.;Outman, Ryan C.;Saag, Kenneth G.
• 通讯作者: Saag, Kenneth G.

Erratum to: Assessing the feasibility of the Effectiveness of Discontinuing Bisphosphonates trial: a pilot study.

勘误表：评估停用双磷酸盐试验有效性的可行性：一项试点研究。

• DOI: 10.1007/s00198-017-4105-1
• 发表时间: 2017
• 期刊: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
• 作者: Wright,NC;Foster,PJ;Mudano,AS;Melnick,JA;Lewiecki,EM;Shergy,WJ;Curtis,JR;Cutter,GR;Danila,MI;Kilgore,ML;Lewis,EC;Morgan,SL;Redden,DT;Warriner,AH;Saag,KG
• 通讯作者: Saag,KG

Assessing the feasibility of the Effectiveness of Discontinuing Bisphosphonates trial: a pilot study.

• DOI: 10.1007/s00198-017-4073-5
• 发表时间: 2017-08
• 期刊: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
• 作者: Wright NC;Foster PJ;Mudano AS;Melnick JA;Lewiecki EM;Shergy WJ;Curtis JR;Cutter GR;Danila MI;Kilgore ML;Lewis EC;Morgan SL;Redden DT;Warriner AH;Saag KG
• 通讯作者: Saag KG