Abstract
BackgroundThe feasibility of effectively analyzing high-density single nucleotide polymorphism (SNP) maps in whole genome scans of complex traits is not known. The purpose of this study was to compare variance components linkage results using different density marker maps in data from the Collaborative Study on the Genetics of Alcoholism (COGA). Marker maps having an average spacing of 10 cM (microsatellite), 0.78 cM (SNP1), and 0.31 cM (SNP2) were used to identify quantitative trait loci (QTLs) affecting maximum number of alcoholic drinks consumed in a 24-hour period (lnmaxalc).ResultsHeritability of lnmaxalc was estimated to be 15%. Multipoint variance components linkage analysis revealed similar linkage patterns among the three marker panels, with the SNP maps consistently yielding higher LOD scores. Robust LOD scores > 1.0 were observed on chromosomes 1 and 13 for all three marker maps. Additional LODs > 1.0 were observed on chromosome 4 with both SNP maps and on chromosomes 18 and 21 with the SNP2 map. Peak LOD scores for lnmaxalc were observed on chromosome 1, although none reached genome-wide statistical significance. Quantile-quantile plots revealed that the multipoint distribution of SNP results appeared to fit the asymptotic null distribution better than the twopoint results.ConclusionIn conclusion, variance-components linkage analysis using high-density SNP maps provided higher LOD scores compared with the standard microsatellite map, similar to studies using nonparametric linkage methods. Widespread application of SNP maps will depend on further improvements in the computational methods implemented in current software packages.
Highlights
The feasibility of effectively analyzing high-density single nucleotide polymorphism (SNP) maps in whole genome scans of complex traits is not known
We chose the self-reported variable, "maximum number of drinks consumed in a 24-hour period," as our alcoholism phenotype
This quantitative trait is correlated with diagnosis of alcoholism and was previously shown to be linked to chromosome 4 in sibling pairs [6]
Summary
The feasibility of effectively analyzing high-density single nucleotide polymorphism (SNP) maps in whole genome scans of complex traits is not known. The purpose of this study was to compare variance components linkage results using different density marker maps in data from the Collaborative Study on the Genetics of Alcoholism (COGA). Marker maps having an average spacing of 10 cM (microsatellite), 0.78 cM (SNP1), and 0.31 cM (SNP2) were used to identify quantitative trait loci (QTLs) affecting maximum number of alcoholic drinks consumed in a 24-hour period (lnmaxalc). Previous linkage studies have identified several chromosomal regions harboring potential genes for alcoholism [1], only a few have been replicated. Studies involving genome-wide linkage scans have used microsatellite markers spaced evenly across the genome at ~10-cM intervals.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
