Co-localization of differentially expressed genes and shared susceptibility loci in human autoimmunity.
Autoimmune diseases arise from complex interactions between environmental and genetic factors. Genetic linkage scans show that different autoimmune diseases share overlapping susceptibility loci. Lymphocytes from individuals with different autoimmune diseases, as well as unaffected first-degree relatives, also share a common gene expression profile. We sought to determine if genes within this autoimmune expression profile were nonrandomly distributed in the genome and if their distribution overlapped with shared disease susceptibility loci. We found that differentially expressed genes were distributed in a nonrandom fashion in chromosomal domains within the genome. Furthermore, positions of these domains were not statistically different from a number of shared autoimmune disease susceptibility loci. To our knowledge, this is the first study showing concordance between gene expression and genetic linkage results in common complex multifactorial human diseases.
Aune
Thomas M
TM
Division of Rheumatology, Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA. thomas.aune@vanderbilt.edu
Parker
Joel S
JS
Maas
Kevin
K
Liu
Zheng
Z
Olsen
Nancy J
NJ
Moore
Jason H
JH
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics*; D015551:Autoimmunity / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged