Program Project in the Genetics of SLE (Robert P. Kimberly, MD; NIAMS P01AR49084)
The overall goal 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, the Program supports four innovative projects and two cores:
Each of these Projects is coordinated through an Administrative Core and a rigorous Genetic Epidemiology and Biostatistics Core (Tiwari, Langefeld, Co-PIs) 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.