Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib–pair linkage analysis

The influence of genetic factors in schizophrenia has been convincingly demonstrated by family, twin and adoption studies^1–3, but the mode of transmission remains uncertain. The reported pattern of recurrence risks suggests a set of interacting loci⁴. Based on prior evidence for linkage on chromosome 6p (K. Kendler, pers. comm.), we have scanned the short arm of chromosome 6 in 54 families for loci predisposing to schizophrenia, using 25 microsatellite markers spanning 60 centiMorgans (cM). Allele sharing identity by descent was examined in affected sib-pairs from these families, followed by multipoint sib-pair linkage analysis. Positive lod scores were obtained over a wide region (D6S470 to D6S271), with a maximum lod score of 2.2 occuring near D6S274, located in 6p22. However, we obtained a lod score of −2 at D6S296, the locus found by others to provide the greatest linkage evidence⁵. At D6S274, we report a positive lod score as do Straub et al.⁵ (individually non-significant). A combined total lod of 3.6–4.0 suggests the possibility of a susceptibility locus in this region. However, methodological differences between our studies makes a firm conclusion difficult.