Evidence for suggestive linkage to schizophrenia with chromosome 6q markers
was previously reported from a two-stage approach. Using nonparametric aff
ected sib pairs (ASP) methods, nominal p-values of 0.00018 and 0.00095 were
obtained in the screening (81 ASPs; 63 independent) and the replication (1
09 ASPs; 87 independent) data sets, respectively. Here, we report a follow-
up study of this 50cM 6q region using 12 microsatellite markers to test for
linkage to schizophrenia. We increased the replication sample size by addi
ng an independent sample of 43 multiplex pedigrees (66 ASPs; 54 independent
). Pairwise and multipoint nonparametric linkage analyses conducted in this
third data set showed evidence consistent with excess sharing in this 6q r
egion, though the statistical level is weaker (p=0.013). When combining bot
h replication data sets (total of 141 independent ASPs), an overall nominal
p-value=0.000014 (LOD=3.82) was obtained. The sibling recurrence risk (hs)
attributed to this putative 6q susceptibility locus is estimated to be 1.9
2. The linkage region could not be narrowed down since LOD score values gre
ater than three were observed within a 13cM region. The length of this regi
on was only slightly reduced (12cM) when using the total sample of independ
ent ASPs (204) obtained from all three data sets. This suggests that very l
arge sample sizes may be needed to narrow down this region by ASP linkage m
ethods. Study of the etiological candidate genes in this region is ongoing.
Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:337-343, 1999. (C) 1994 Wil
ey-Liss, Inc.