GENOMEWIDE SCAN OF MULTIPLE-SCLEROSIS IN FINNISH MULTIPLEX FAMILIES

Multiple sclerosis (MS) is a neurological, demyelinating disorder with a putative autoimmune etiology. It is thought to be a multifactorial disease with a complex mode of inheritance. Here we report the results of a two-stage genomewide scan for loci predisposing to MS. The first stage of the screen, with a low-resolution map, was performed in a se lection of 16 pedigrees collected from an isolated Finnish population. Multipoint, nonparametric linkage analysis of the 328 markers did not reveal statistically significant results. However, 10 slightly intere sting regions (P = .1-.15) emerged, including our previous findings of the HLA complex on Gp21. and a putative locus on 5p14-p12. Fight of t hese novel regions were further analyzed by use of denser marker maps, in the second stage of the scan. For the chromosomal regions 4cen, 11 tel, and 17q, the statistical significance increased, but not conclusi vely; for 2q32 and 10q21, the statistical significance did not change. Accordingly, genotyping of the high-density markers in these regions was performed, and the data were analyzed by use of two-point, paramet ric linkage analysis using the complete pedigree information of the 21 Finnish multiplex families. We detected suggestive evidence for a pre disposing locus on chromosomal region 17q22-q24. Several markers on 17 q22-q24 yielded positive LOD scores, with the maximum LOD score (Z(max )) occurring with D17S807 (Z(max) = 2.8, theta = .04; dominant model). Interestingly, a suggestive linkage between MS and the markers on 17q 22-q24 was also revealed by a recent genomewide scan in MS families fr om the United Kingdom.