TY - JOUR
T1 - Evidence for linkage and association to alcohol dependence on chromosome 19
AU - Valdes, Ana M.
AU - McWeeney, Shannon K.
AU - Thomson, Glenys
PY - 1999
Y1 - 1999
N2 - An association study on markers showing suggestive evidence for linkage to severe alcoholism was performed on the Collaborative Study on the Genetics of Alcoholism (COGA) data set. Our linkage study was restricted to the autosomal markers on chromosomes 2, 3, 4, 13, and 19, with low homozygosity (below 30%) and high identity-by-state sharing in affected sib pairs (ASPs). We used a strict phenotype definition, only individuals diagnosed as affected both on the ALDX1 (COGA criterion) and ALDX2 (ICD-10) scales were used in the analyses. Linkage was assessed by excess identity-by-descent allele sharing in ASPs. The strongest evidence of linkage was detected on chromosome 19, in particular at markers D19S49 (p < 0.0001) and D19S431 (p < 0.002). An association study of allele and haplotype data was then carried out on chromosome 19 markers using affected-family-based controls. A haplotype defined by alleles at markers D19S49, D19S43, and D19S200 in chromosome 19 shows significant association (p < 0.003, odds ratio 2.82). Further, significant differences were observed in the distribution of the harm avoidance subscale among genotypes defined by D19S49 (p < 0.0001). These results provide evidence for the existence of a locus in chromosome 19 potentially involved in alcohol dependence susceptibility.
AB - An association study on markers showing suggestive evidence for linkage to severe alcoholism was performed on the Collaborative Study on the Genetics of Alcoholism (COGA) data set. Our linkage study was restricted to the autosomal markers on chromosomes 2, 3, 4, 13, and 19, with low homozygosity (below 30%) and high identity-by-state sharing in affected sib pairs (ASPs). We used a strict phenotype definition, only individuals diagnosed as affected both on the ALDX1 (COGA criterion) and ALDX2 (ICD-10) scales were used in the analyses. Linkage was assessed by excess identity-by-descent allele sharing in ASPs. The strongest evidence of linkage was detected on chromosome 19, in particular at markers D19S49 (p < 0.0001) and D19S431 (p < 0.002). An association study of allele and haplotype data was then carried out on chromosome 19 markers using affected-family-based controls. A haplotype defined by alleles at markers D19S49, D19S43, and D19S200 in chromosome 19 shows significant association (p < 0.003, odds ratio 2.82). Further, significant differences were observed in the distribution of the harm avoidance subscale among genotypes defined by D19S49 (p < 0.0001). These results provide evidence for the existence of a locus in chromosome 19 potentially involved in alcohol dependence susceptibility.
KW - Affected family based controls
KW - Harm avoidance
UR - http://www.scopus.com/inward/record.url?scp=0032709420&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032709420&partnerID=8YFLogxK
U2 - 10.1002/gepi.1370170762
DO - 10.1002/gepi.1370170762
M3 - Article
C2 - 10597464
AN - SCOPUS:0032709420
SN - 0741-0395
VL - 17
SP - S367-S372
JO - Genetic Epidemiology
JF - Genetic Epidemiology
IS - SUPPL. 1
ER -