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Two-dimensional linkage analyses of rheumatoid arthritis.

Mukhopadhyay N, Halder I, Bhattacharjee S, Weeks DE - BMC Proc (2007)

Bottom Line: Potentially interesting regions were first identified by testing for major gene effects using non-parametric linkage methods.We subsequently analyzed the selected regions in a pairwise manner to detect gene x gene interactions influencing RA using a recently developed two-dimensional linkage method.We found evidence of interacting loci on chromosomes 5, 6, and 18.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, A300 Crabtree Hall, 130 DeSoto Street, Pittsburgh, Pennsylvania 15261, USA. nandita@pitt.edu

ABSTRACT
Rheumatoid arthritis (RA) is a multifactorial disease with complex genetic etiology, about which little is known. Here, we apply a two-stage procedure in which a quick first-stage analysis was used to narrow down targets for a more thorough and detailed testing for gene x gene interaction. Potentially interesting regions were first identified by testing for major gene effects using non-parametric linkage methods. To select regions of interest, we first tested for linkage to three different RA-related traits one at a time: RA affection status and the quantitative phenotypes rheumatoid factor IgM and anti-cyclic citrullinated peptide levels. These linkage analyses identified regions on chromosomes 3, 5, 6, 8, 16, 18, 19, and 20. We subsequently analyzed the selected regions in a pairwise manner to detect gene x gene interactions influencing RA using a recently developed two-dimensional linkage method. We found evidence of interacting loci on chromosomes 5, 6, and 18.

No MeSH data available.


Related in: MedlinePlus

Single-locus contributions of chromosome 6 SNPs vs. other SNPs. Dark grey, single-locus LOD scores of the chromosome 6 SNP; light gray, single-locus LOD scores of the other SNP; unshaded, the interaction contribution. Numbers in parentheses on the X-axis indicate separate regions on a single chromosome.
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Figure 1: Single-locus contributions of chromosome 6 SNPs vs. other SNPs. Dark grey, single-locus LOD scores of the chromosome 6 SNP; light gray, single-locus LOD scores of the other SNP; unshaded, the interaction contribution. Numbers in parentheses on the X-axis indicate separate regions on a single chromosome.

Mentions: Figure 1 contains two-locus results of SNPs on chromosome 6 with SNPs on other chromosomes. Because the two-locus analysis estimates interaction effects after fixing the single-locus LOD scores for each of the two loci, comparing the remainder of the general LOD score to the individual contributions provides us with a measure of gene × gene interaction effects. The total height of each bar represents the maximum two-locus LOD score obtained for the general model, with the dark shaded area representing the marginal score for the chromosome 6 SNP, the lightly shaded area being the marginal contribution of the second SNP, and unshaded area being the remaining contribution, including two-locus interaction effects. All analyses involving region 2 on chromosome 6 showed highly elevated LOD scores in the two-locus analysis, and most were due to the marginal single-locus contributions of SNPs on chromosome 6. The chromosome 5-chromosome 6:region 1 locus pairs have marginal contributions from both loci, as well as a total additive effect. In region 3 of chromosome 6 the general model LOD scores appear to be larger than either single-locus LOD score. The actual LOD score values are given in rows two and three of Table 2.


Two-dimensional linkage analyses of rheumatoid arthritis.

Mukhopadhyay N, Halder I, Bhattacharjee S, Weeks DE - BMC Proc (2007)

Single-locus contributions of chromosome 6 SNPs vs. other SNPs. Dark grey, single-locus LOD scores of the chromosome 6 SNP; light gray, single-locus LOD scores of the other SNP; unshaded, the interaction contribution. Numbers in parentheses on the X-axis indicate separate regions on a single chromosome.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2367460&req=5

Figure 1: Single-locus contributions of chromosome 6 SNPs vs. other SNPs. Dark grey, single-locus LOD scores of the chromosome 6 SNP; light gray, single-locus LOD scores of the other SNP; unshaded, the interaction contribution. Numbers in parentheses on the X-axis indicate separate regions on a single chromosome.
Mentions: Figure 1 contains two-locus results of SNPs on chromosome 6 with SNPs on other chromosomes. Because the two-locus analysis estimates interaction effects after fixing the single-locus LOD scores for each of the two loci, comparing the remainder of the general LOD score to the individual contributions provides us with a measure of gene × gene interaction effects. The total height of each bar represents the maximum two-locus LOD score obtained for the general model, with the dark shaded area representing the marginal score for the chromosome 6 SNP, the lightly shaded area being the marginal contribution of the second SNP, and unshaded area being the remaining contribution, including two-locus interaction effects. All analyses involving region 2 on chromosome 6 showed highly elevated LOD scores in the two-locus analysis, and most were due to the marginal single-locus contributions of SNPs on chromosome 6. The chromosome 5-chromosome 6:region 1 locus pairs have marginal contributions from both loci, as well as a total additive effect. In region 3 of chromosome 6 the general model LOD scores appear to be larger than either single-locus LOD score. The actual LOD score values are given in rows two and three of Table 2.

Bottom Line: Potentially interesting regions were first identified by testing for major gene effects using non-parametric linkage methods.We subsequently analyzed the selected regions in a pairwise manner to detect gene x gene interactions influencing RA using a recently developed two-dimensional linkage method.We found evidence of interacting loci on chromosomes 5, 6, and 18.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, A300 Crabtree Hall, 130 DeSoto Street, Pittsburgh, Pennsylvania 15261, USA. nandita@pitt.edu

ABSTRACT
Rheumatoid arthritis (RA) is a multifactorial disease with complex genetic etiology, about which little is known. Here, we apply a two-stage procedure in which a quick first-stage analysis was used to narrow down targets for a more thorough and detailed testing for gene x gene interaction. Potentially interesting regions were first identified by testing for major gene effects using non-parametric linkage methods. To select regions of interest, we first tested for linkage to three different RA-related traits one at a time: RA affection status and the quantitative phenotypes rheumatoid factor IgM and anti-cyclic citrullinated peptide levels. These linkage analyses identified regions on chromosomes 3, 5, 6, 8, 16, 18, 19, and 20. We subsequently analyzed the selected regions in a pairwise manner to detect gene x gene interactions influencing RA using a recently developed two-dimensional linkage method. We found evidence of interacting loci on chromosomes 5, 6, and 18.

No MeSH data available.


Related in: MedlinePlus