title: Genetic vectors as a tool in association studies: definitions and application for study of rheumatoid arthritis.
abstract: To identify putative relations between different genetic factors in the human genome in the development of common complex disease, we mapped the genetic data to an ensemble of spin chains and analysed the data as a quantum system. Each SNP is considered as a spin with three states corresponding to possible genotypes. The combined genotype represents a multispin state, described by the product of individual-spin states. Each person is characterized by a single genetic vector (GV) and individuals with identical GVs comprise the GV group. This consolidation of genotypes into GVs provides integration of multiple genetic variants for a single statistical test and excludes ambiguity of biological interpretation known for allele and haplotype associations. We analyzed two independent cohorts, with 2633 rheumatoid arthritis cases and 2108 healthy controls, and data for 6 SNPs from the HTR2A locus plus shared epitope allele. We found that GVs based on selected markers are highly informative and overlap for 98.3% of the healthy population between two cohorts. Interestingly, some of the GV groups contain either only controls or only cases, thus demonstrating extreme susceptibility or protection features. By using this new approach we confirmed previously detected univariate associations and demonstrated the most efficient selection of SNPs for combined analyses for functional studies.
authors.affiliation: Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, CMM L8:04, 17176 Stockholm, Sweden ; L.V. Kirensky Institute of Physics, Akademgorodok 50, Krasnoyarsk 660036, Russia.
authors.forename: Igor
authors.initials: I
authors.lastname: Sandalov
authors.affiliation: Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, CMM L8:04, 17176 Stockholm, Sweden.
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
references.citation: Stat Sci. 2009 Nov 1;24(4):489-502
references.pmid: 20543902
references.citation: Arthritis Rheum. 2009 Apr;60(4):924-30
references.pmid: 19333936
references.citation: Arthritis Rheum. 2004 Mar;50(3):736-41
references.pmid: 15022313
references.citation: Am J Hum Genet. 2001 Apr;68(4):927-36
references.pmid: 11254450
references.citation: Brief Bioinform. 2012 Jan;13(1):1-19
references.pmid: 21441561
references.citation: Arthritis Rheum. 1988 Mar;31(3):315-24
references.pmid: 3358796
references.citation: Arthritis Rheum. 2006 Jan;54(1):38-46
references.pmid: 16385494
references.citation: Ann Rheum Dis. 2008 Aug;67(8):1111-5
references.pmid: 18006541