Marker-to-marker linkage disequilibrium on chromosomes 5q, 6p, and 8p in Irish high-density schizophrenia pedigrees

Abstract

Linkage disequilibrium (LD) is a potentially powerful tool for the localization of disease genes for complex disorders. Most prior studies of the relationship between genetic distance and LD have examined only very short distances, focusing on the role of LD in fine-mapping and positional cloning. We examine here the relationship between marker-to-marker (M-M) LD and somewhat greater genetic distances. We analyzed 622 M-M pairings on chromosomes 6p, 8p, and 5q in 265 native Irish pedigrees ascertained for a high density of schizophrenia. LD, significant at the 5% level, was found for 96% of all M-M pairings within 0.5 cM, for 67% within 0.5-1 cM, for 35% within 1-2 cM, for 15% within 2-4 cM, for 8% within 5-10 cM, and for 7% above 10 cM. Thus, in Irish families selected for a high density of schizophrenia, M-M LD may be very common within 0.5 cM and frequent up to distances of 2 cM.

Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer

“…102,103 However, a published study has not been able to find significant evidence for linkage on 8p region. 104 It is important to take into consideration that Kendler et al 105 found an association between 8p22-21 locus and some clinical features in 265 multiplex schizophrenia pedigrees. More specifically, affected individuals from families with evidence of linkage to 8p had significantly more affective deterioration and thought disorders, a worse outcome, and fewer depressive symptoms than affected individuals from the other families in the study.…”

Genomewide linkage study in the Irish affected sib pair study of alcohol dependence: evidence for a susceptibility region for symptoms of alcohol dependence on chromosome 4

“…16 In addition, although Ireland is not a genetic isolate, the degree of genetic variation in Ireland is substantially less than in a general US sample. 17 The current Irish population derives largely from a series of prehistoric Celtic invasions, supplemented in the last 400 years by English and Scottish settlement.…”

Linkage disequilibrium mapping at DAT1, DRD5 and DBH narrows the search for ADHD susceptibility alleles at these loci

“…In the Irish context, marker-to-marker analysis of association conducted between adjacent microsatellite markers on chromosome 5, 6 and 8 showed significant association for 96% of all markers within 0.5 cM of each other, 67% within 0.5-1 cM, 35% within 1-2 cM, 15% within 2-4 cM, 8% within 5-10 cM and 7% over 10 cM. 15 This suggests that this population may have certain advantages in a positional cloning experiment. However, extensive LD would be a disadvantage for fine mapping of association, for example, at candidate gene loci.…”