Linkage analysis of alcoholism-related electrophysiological phenotypes: genome scans with microsatellites compared to single-nucleotide polymorphisms.
P300 amplitude is an electrophysiological quantitative trait that is correlated with both alcoholism and smoking status. Using the Collaborative Study on the Genetics of Alcoholism data, we performed model-free linkage analysis to investigate the relationship between alcoholism, P300 amplitude, and habitual smoking. We also analyzed the effect of parent-of-origin on alcoholism, and utilized both microsatellites (MS) markers and single-nucleotide polymorphisms (SNPs). We found significant evidence of linkage for alcoholism to chromosome 10; inclusion of P300 amplitude as a covariate provided additional evidence of linkage to chromosome 12. This same region on chromosome 12 showed some evidence for a parent-of-origin effect. We found evidence of linkage for the P300 phenotype to chromosome 7 in non-smokers, and to chromosome 17 in alcoholics. The effects of alcoholism and habitual smoking on P300 amplitude appear to have separate genetic determinants. Overall, there were few differences between MS and SNP genome scans. The use of covariates and parent-of-origin effects allowed detection of linkage not seen otherwise.
Bautista
Jocelyn F
JF
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA. jbautista@darwin.cwru.edu
Quade
Shannon R E
SR
Parrado
Antonio R
AR
Goddard
Katrina A B
KA
D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology*; D002874:Chromosome Mapping; D055724:Electrophysiological Phenomena / Q000235:genetics*; D018913:Event-Related Potentials, P300 / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D008957:Models, Genetic; D010290:Parents; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D035781:Siblings; D012907:Smoking / Q000235:genetics