The overall goal of this competitive renewal of our Program Project in the Genetics of SLE is to identify the genes responsible for susceptibility to and severity of SLE in ethnic minorities. Our scientific strategy involves three approaches: (1) to use genome-wide linkage data, developed during the first project period, to define regions with significant genetic effects, to use fine mapping of single nucleotide polymorphisms to narrow the interval, and then to focus on candidate genes and their haplotypes to identify risk alleles (haplotypes);(2) to use genotypic information, developed during the first project period, in both families and collections of individuals on established candidate gene families which suggest a role for copy number variation and to establish the range of variation and its contribution to SLE;and (3) to examine the genetic contribution to disease severity and outcome over time by continuing to build our longitudinal collaborative cohort (PROFILE) and assessing the impact of genotype on the phenotype of clinical outcomes. To implement our scientific strategy, we propose four projects and two cores. Project No. 1 (Kimberly, PI) will examine the role of structural variants (copy number variation) in the classical Fc receptor cluster in contributing to SLE risk and outcomes in different ethnic groups. Project No. 2 (Harley, PI) will define the strong association at 12q24 with SLE in Hispanics and test the hypothesis that this effect reflects variants of TCF1. Project No. 3 (Nath, PI) will use an admixture mapping approach to discover new genes contributing to lupus in African Americans and to test their contribution to the more severe outcome in this ethnic group. And Project No. 4 (Alarcon, PI) will examine the relationship between biologic ancestry, SES variables and outcomes in a test of gene environment relationships. Each of these Projects is coordinated through an Administrative Core and a vigorous Genetic Epidemiology and Biostatistics Core which serves each project. Working together, the investigators of this P01 anticipate making major advances in our understanding of the genetic variants underlying SLE in ethnic minorities.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAR1-MLB-G (J1))
Program Officer
Wang, Yan Z
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Alabama Birmingham
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Langefeld, Carl D; Ainsworth, Hannah C; Cunninghame Graham, Deborah S et al. (2017) Transancestral mapping and genetic load in systemic lupus erythematosus. Nat Commun 8:16021
Alarcón-Riquelme, Marta E; Ziegler, Julie T; Molineros, Julio et al. (2016) Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture. Arthritis Rheumatol 68:932-43
Deng, Yun; Zhao, Jian; Sakurai, Daisuke et al. (2016) Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production. Ann Rheum Dis 75:2007-2013
Lessard, Christopher J; Sajuthi, Satria; Zhao, Jian et al. (2016) Identification of a Systemic Lupus Erythematosus Risk Locus Spanning ATG16L2, FCHSD2, and P2RY2 in Koreans. Arthritis Rheumatol 68:1197-1209
Zhao, Jian; Giles, Brendan M; Taylor, Rhonda L et al. (2016) Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA. Ann Rheum Dis 75:242-52
Taylor, Rhonda L; Cruickshank, Mark N; Karimi, Mahdad et al. (2016) Focused transcription from the human CR2/CD21 core promoter is regulated by synergistic activity of TATA and Initiator elements in mature B cells. Cell Mol Immunol 13:119-31
Liu, Ke; Kurien, Biji T; Zimmerman, Sarah L et al. (2016) X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome. Arthritis Rheumatol 68:1290-1300
Kottyan, Leah C; Zoller, Erin E; Bene, Jessica et al. (2015) The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share. Hum Mol Genet 24:582-96
Lu, Xiaoming; Zoller, Erin E; Weirauch, Matthew T et al. (2015) Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression. Am J Hum Genet 96:731-9
Huang, Chengrui; Haritunians, Talin; Okou, David T et al. (2015) Characterization of genetic loci that affect susceptibility to inflammatory bowel diseases in African Americans. Gastroenterology 149:1575-1586

Showing the most recent 10 out of 213 publications