LINKAGE STUDY OF PROSTATE CANCER IN LARGE HIGH-RISK AFRICAN AMERICAN FAMILIES.
Document Type
Presentation
Start Date
22-10-2010 1:45 PM
End Date
22-10-2010 2:00 PM
Description
Prostate cancer is a complex multi-allelic disease and the most common malignancy in men throughout the world. Incidence of prostate cancer in African-American men is almost twice compared with Caucasian men and African-American men are more than twice as likely to die from this disease Thus far, several disease susceptibility loci have been identified for this cancer but definite locus-specific information is not established due to genetic heterogeneity. In the present study, genotyping was performed on 15 high-risk (~ 3 affected/family) African-American families using 6,090 SNP markers. An lnfinium II Humanlinkage-12 panel (lllumina, Inc.) was used. This panel is optimized for linkage detection for both monogenic and polygenic disorders; SNPs are distributed on every chromosome with an average gap of 441 Kb and 0.58 cM. Sample genotypes were imported into BeadStudio version 3.3.7 and a proprietary calling algorithm was used; SNPs which failed after manual clustering were discarded. SNPs with less than 95% call rate were also removed. SNPs were checked for adherence to Hardy-Weinberg Equilibrium and adequate minor allele frequency (MAF>0.05) and removed accordingly. Mendelian inconsistencies were checked within families and SNPs or individuals which had >5% errors were removed. To avoid false positive results, pruning of released SNPs was performed using PLINK and SNPs in high linkage disequilibrium (LD) were removed. Linkage analysis was performed with Merlin using both model-based (parametric) and model-free (non-parametric) methods. Preliminary analysis shows evidence of linkage on chromosomes 1, 3, 4, 8 and 12 (maximum HLOD or heterogeneity lod score= 2.0, p-value = 0.002; maximum NPL Lod score= 1.427, pvalue = 0.005). Data analysis with alternative models and LO-based pruning options is ongoing. We will also use ordered subset analysis to include covariates of prostate cancer in the analysis, such as, prostate specific antigen (PSA), 'age of onset' and/or Gleason scores obtained from the pathological reports of affected individuals.
Recommended Citation
Ledet, Elisa and Mandal, D. M., "LINKAGE STUDY OF PROSTATE CANCER IN LARGE HIGH-RISK AFRICAN AMERICAN FAMILIES." (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 4.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/presentation2/4
LINKAGE STUDY OF PROSTATE CANCER IN LARGE HIGH-RISK AFRICAN AMERICAN FAMILIES.
Prostate cancer is a complex multi-allelic disease and the most common malignancy in men throughout the world. Incidence of prostate cancer in African-American men is almost twice compared with Caucasian men and African-American men are more than twice as likely to die from this disease Thus far, several disease susceptibility loci have been identified for this cancer but definite locus-specific information is not established due to genetic heterogeneity. In the present study, genotyping was performed on 15 high-risk (~ 3 affected/family) African-American families using 6,090 SNP markers. An lnfinium II Humanlinkage-12 panel (lllumina, Inc.) was used. This panel is optimized for linkage detection for both monogenic and polygenic disorders; SNPs are distributed on every chromosome with an average gap of 441 Kb and 0.58 cM. Sample genotypes were imported into BeadStudio version 3.3.7 and a proprietary calling algorithm was used; SNPs which failed after manual clustering were discarded. SNPs with less than 95% call rate were also removed. SNPs were checked for adherence to Hardy-Weinberg Equilibrium and adequate minor allele frequency (MAF>0.05) and removed accordingly. Mendelian inconsistencies were checked within families and SNPs or individuals which had >5% errors were removed. To avoid false positive results, pruning of released SNPs was performed using PLINK and SNPs in high linkage disequilibrium (LD) were removed. Linkage analysis was performed with Merlin using both model-based (parametric) and model-free (non-parametric) methods. Preliminary analysis shows evidence of linkage on chromosomes 1, 3, 4, 8 and 12 (maximum HLOD or heterogeneity lod score= 2.0, p-value = 0.002; maximum NPL Lod score= 1.427, pvalue = 0.005). Data analysis with alternative models and LO-based pruning options is ongoing. We will also use ordered subset analysis to include covariates of prostate cancer in the analysis, such as, prostate specific antigen (PSA), 'age of onset' and/or Gleason scores obtained from the pathological reports of affected individuals.
Comments
See abstract book page 40