EXCLUSION OF LINKAGE BETWEEN ALCOHOLISM AND THE MNS BLOOD-GROUP REGION ON CHROMOSOME 4Q IN MULTIPLEX FAMILIES

Polymorphic DNA markers on the long arm of chromosome 4 were used to e xamine Linkage to alcoholism in 20 multiplex pedigrees. Fifteen loci w ere determined for 124 individuals. Lod scores were calculated assumin g both dominant and recessive disease modes of inheritance, utilizing incidence data by age and gender that allow for correction for variabl e age of onset and frequency of the disorder by gender. Under the assu mption that alcoholism is homogeneous in this set of pedigrees, and th at a recessive mode with age and gender correction is the most appropr iate, the total lod scores for all families combined were uniformly lo wer than -2.0. This suggests an absence of linkage between the putativ e alcoholism susceptibility gene and markers in the region of the MNS blood group (4q28-31), a region for which we had previously found sugg estive evidence of linkage to alcoholism. The 100 cM span of chromosom e 4 studied includes the class I alcohol dehydrogenase (ADH) loci. Usi ng the recessive mode, no evidence for linkage to alcoholism was found for the markers tested, which spanned almost the entire long arm of c hromosome 4. Under the dominant mode, no evidence for linkage could be found for several of the markers. (C) 1995 Wiley-Liss, Inc.