Abstract

This application is a competitive renewal of a project which has the overall goal of identifying susceptibility genes for rheumatoid arthritis which lie outside of the major histocompatibility complex (MH( We have completed a genome wide screen for allele sharing on an initial population of 300 affected sibling pairs with RA. We have identified five markers with evidence of linkage at the p Specific Aim 1 : Confirmation of linkage to rheumatoid arthritis and narrowing of the genetic interval in genetic regions showing preliminary evidence of linkage. We are currently pursuing a replication of our initial linkage results in a second set of 300 sibling pairs. Where evidence of linkage continues to persist, dense mapping for linkage around regions of interest will be performed on a data set of 1,000 sibling pairs.
Specific Aim 2 : Fine mapping of candidate regions using methods dependent on linkage disequilibrium. Selected regions will be supported by the replication and fi linkage mapping in specific aim 1. Up to three of these regions will be further narrowed using two approaches based on linkage disequilibrium. First, one affected member from each sib pair family will be used in case control studies. Second, an independent population of 1,000 RA patients and both parents will be analyzed by transmission disequilibrium testing. These studies will incorporate haplotypic analyses.
Specific Aim 3. Identification and analysis of candidate genes in regions showing linkage and association with RA. We assume that there will be full availability of the human genome sequence by the time we seriously address the specific aim. The end game of gene identification will involve repeated association studies with specific polymorphisms of interest in candidate genes, in conjunction with detailed haplotypic analysis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR044422-08
Application #
6833271
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Serrate-Sztein, Susana
Project Start
1997-07-05
Project End
2007-06-30
Budget Start
2004-07-01
Budget End
2007-06-30
Support Year
8
Fiscal Year
2004
Total Cost
$583,778
Indirect Cost

  Institution

Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
110565913
City
Manhasset
State
NY
Country
United States
Zip Code
11030

  Publications

Zou, Qi-Lei; You, Xiao-Ping; Li, Jian-Long et al. (2018) A powerful parent-of-origin effects test for qualitative traits on X chromosome in general pedigrees. BMC Bioinformatics 19:8
Li, Jian-Long; Wang, Peng; Fung, Wing Kam et al. (2017) Generalized disequilibrium test for association in qualitative traits incorporating imprinting effects based on extended pedigrees. BMC Genet 18:90
Wei, Wen-Hua; Loh, Chia-Yin; Worthington, Jane et al. (2016) Immunochip Analyses of Epistasis in Rheumatoid Arthritis Confirm Multiple Interactions within MHC and Suggest Novel Non-MHC Epistatic Signals. J Rheumatol 43:839-45
You, Xiao-Ping; Zou, Qi-Lei; Li, Jian-Long et al. (2015) Likelihood Ratio Test for Excess Homozygosity at Marker Loci on X Chromosome. PLoS One 10:e0145032
Li, Qizhai; Hu, Jiyuan; Ding, Juan et al. (2014) Fisher's method of combining dependent statistics using generalizations of the gamma distribution with applications to genetic pleiotropic associations. Biostatistics 15:284-95
Veal, Colin D; Reekie, Katherine E; Lorentzen, Johnny C et al. (2014) A 129-kb deletion on chromosome 12 confers substantial protection against rheumatoid arthritis, implicating the gene SLC2A3. Hum Mutat 35:248-56
Taliun, Daniel; Gamper, Johann; Pattaro, Cristian (2014) Efficient haplotype block recognition of very long and dense genetic sequences. BMC Bioinformatics 15:10
Knevel, Rachel; Klein, Kerstin; Somers, Klaartje et al. (2014) Identification of a genetic variant for joint damage progression in autoantibody-positive rheumatoid arthritis. Ann Rheum Dis 73:2038-46
Guo, Xuan; Meng, Yu; Yu, Ning et al. (2014) Cloud computing for detecting high-order genome-wide epistatic interaction via dynamic clustering. BMC Bioinformatics 15:102
Liu, Li; Zhang, Donghui; Liu, Hong et al. (2013) Robust methods for population stratification in genome wide association studies. BMC Bioinformatics 14:132

Showing the most recent 10 out of 99 publications