Kristina Allen-Brady1, Lisa A Cannon-Albright2, James M Farnham3, Peggy A Norton4. 1. Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT. Electronic address: kristina.allen@utah.edu. 2. Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT; Research and Development Service, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT. 3. Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT. 4. Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, UT.
Abstract
OBJECTIVE: We conducted a genomewide linkage analysis to identify pelvic organ prolapse (POP) predisposition genes using a resource of high-risk POP pedigrees. STUDY DESIGN: Cases are defined as women who reported bothersome symptoms of POP based on standardized symptom questions (Pelvic Floor Distress Inventory, moderately or quite bothered), and/or received treatment for POP documented in medical records. Our complete pedigree resource contains 299 familial POP cases in 83 high-risk pedigrees. Genotype data were obtained from Illumina HumanHap550, 610Q, the Human1M-Duo, Human Omni1-Quad, or the Human Omni 2.5 platforms. A set of single nucleotide polymorphism markers common to all platforms was identified and markers in high linkage disequilibrium were removed. We performed a genomewide linkage analysis under general dominant and recessive models using a Markov chain, Monte Carlo linkage analysis method implemented in MCLINK (University of Utah) software. Because 70 individuals in 32 pedigrees were used in a previously published linkage analysis for a phenotype of POP requiring treatment/surgery, we also performed linkage only including the 225 newly recruited and genotyped cases in 61 pedigrees. RESULTS: Linkage analysis using our complete pedigree resource for the loosened criteria of bothersome POP showed evidence for significant genomewide linkage on chromosome 10q24-26 (recessive model, maximum heterogeneity logarithm of odds 3.4); suggestive evidence was identified on chromosomes 6 and 17, and an additional region on chromosome 10. In the subset of only the newly recruited familial POP cases, significant evidence for genomewide linkage was observed on chromosome 17q25 (recessive model, maximum heterogeneity logarithm of odds 3.3), and suggestive evidence for linkage was observed on chromosomes 10 and 11. Neither analysis duplicated the previously published linkage evidence for the POP requiring treatment/surgery phenotype observed on chromosome 9. CONCLUSION: While the etiology of this common condition is unknown, this study provides evidence that loci on chromosomes 10q and 17q may contribute to POP etiology.
OBJECTIVE: We conducted a genomewide linkage analysis to identify pelvic organ prolapse (POP) predisposition genes using a resource of high-risk POP pedigrees. STUDY DESIGN: Cases are defined as women who reported bothersome symptoms of POP based on standardized symptom questions (Pelvic Floor Distress Inventory, moderately or quite bothered), and/or received treatment for POP documented in medical records. Our complete pedigree resource contains 299 familial POP cases in 83 high-risk pedigrees. Genotype data were obtained from Illumina HumanHap550, 610Q, the Human1M-Duo, Human Omni1-Quad, or the Human Omni 2.5 platforms. A set of single nucleotide polymorphism markers common to all platforms was identified and markers in high linkage disequilibrium were removed. We performed a genomewide linkage analysis under general dominant and recessive models using a Markov chain, Monte Carlo linkage analysis method implemented in MCLINK (University of Utah) software. Because 70 individuals in 32 pedigrees were used in a previously published linkage analysis for a phenotype of POP requiring treatment/surgery, we also performed linkage only including the 225 newly recruited and genotyped cases in 61 pedigrees. RESULTS: Linkage analysis using our complete pedigree resource for the loosened criteria of bothersome POP showed evidence for significant genomewide linkage on chromosome 10q24-26 (recessive model, maximum heterogeneity logarithm of odds 3.4); suggestive evidence was identified on chromosomes 6 and 17, and an additional region on chromosome 10. In the subset of only the newly recruited familial POP cases, significant evidence for genomewide linkage was observed on chromosome 17q25 (recessive model, maximum heterogeneity logarithm of odds 3.3), and suggestive evidence for linkage was observed on chromosomes 10 and 11. Neither analysis duplicated the previously published linkage evidence for the POP requiring treatment/surgery phenotype observed on chromosome 9. CONCLUSION: While the etiology of this common condition is unknown, this study provides evidence that loci on chromosomes 10q and 17q may contribute to POP etiology.
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