Genetic Architecture of Rheumatoid Arthritis in African-Americans

非裔美国人类风湿关节炎的遗传结构

基本信息

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
项目类别：
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

项目摘要

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风湿性疾病遗传学的独立资助的研究者，尤其是类风湿关节炎（RA）。为了实现这一目标，申请人提出了一项职业发展计划，重点是在流行病学和统计遗传学方法原理中进行教学培训，通过向临床研究中的公共卫生科学硕士开设课程。此外，她还将获得生物信息学方面的动手培训。她将精通使用最先进的统计技术，这些技术可以适应大型遗传数据集带来的独特挑战。该候选人通过成功的指导和流变学，流行病学和统计遗传学的成功指导和学术成就来召集一个强大的跨学科指导团队。这项受过指导的以患者为导向的研究职业发展奖的研究组成部分提议确定非裔美国人RA风险和RA风险和严重性的遗传关联，并使用临床和基因组数据来建立RA风险和结果的预测模型。来自NIH资助的财团可获得约1000名非裔美国人RA参与者和约1700名非裔美国人控制的数据，用于对具有RA（Clear）注册表的非洲裔美国人以及本地和国家合作的纵向评估。基因分型数据将可从免疫光切除，这是一个约200,000个稀有且常见的单核苷酸多态性（SNP）的自定义阵列，由免疫化联盟开发。免疫光包含从高加索和亚洲人群中通过GWAS策略在自身免疫性疾病中发现的最密切相关的制造商中选择的SNP，包括RA，1型糖尿病，狼疮，腹腔疾病，腹腔疾病，自身免疫性甲状腺病，炎症性肠道疾病，炎症性肠道病，甲基甲基疾病性疾病，顺式疾病和其他疾病。目前正在使用Lou Bridges博士提供的UAB的机构资金进行基因分型（请参阅Peter Gregersen博士的信），并将在此K23申请的要求开始日期之前获得。该研究的科学目的是：1）确定在欧洲和亚洲人群中验证的自身免疫的遗传标志是否会影响非裔美国人发展RA的风险； 2）确定RA易感性的遗传标志物是否在非裔美国人的RA的放射线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RA风险和结果的遗传影响的理解，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

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
影响因子：
0
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
影响因子：
0
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
影响因子：
0
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