Genetic factors in fibromyalgia syndrome (FMS) have been suspected because of familial clustering of this disorder. Pellegrino, et al had studied 17 patients with FMS from a support group and their 50 parents and siblings and found that 52% of these relatives had FMS (Arch Phys Med Rehabil 1989; 70:61-63); they also concluded that FMS is an autosomal dominant disease. Buskila, et al investigated 30 FMS patients and 91 of their first-degree relatives (FDR) and reported that 26% of the FDR had FMS (J Rheumatol 1997; 24:941-44). Rosenblatt et al diagnosed FMS among 71% mothers of 34 children with FMS (J Musculoskel Pain 1995; 2 (suppl 1): 118). However these reports of familial aggregation do not confirm role of genetics in FMS because of the influence of environmental factors in such aggregation. 

Studies of an association between FMS and an HLA allele are inclusive. Burda, et al studied only 18 patients with FMS and 23 normal controls and found a significant association with DR4 (Clin Exp Rheumatol 1986; 4:355-7). Branco, et al investigated 52 FMS patients and 869 normal controls and found an association of HLA B58, DR8 and DR5 (J Musculoskel Pain 1996; 4:21-7). However, Horven et al, in an earlier report, found no HLA association among 60 patients with FMS and 159 normal controls (J Rheumatol 1992; 19:1269-70).

We investigated 40 multicase families with FMS and sought to determine genetic linkage of FMS with HLA. Such linkage studies avoid the biases involved in HLA association studied. Eighty-five affected and 21 unaffected members of 41 sibships were studied clinically and by HLA typing. We analyzed data by model-free linkage method which examine identity-by-descent (IBD) sharing among sets of relatives and do not require specification of the mode of inheritance. Sibship analysis showed a weak (P=0.028) linkage of FMS to the HLA region.

In collaboration with the Case Western Reserve University, Cleveland, we now plan to study an additional 120 families to confirm our earlier report, and importantly, to perform a genome scan on the family members of our earlier 40 and new 120 (a total of 160 families) for over 200 genetic markers at 20 cM intervals throughout the genome. We will also include markers close to selected candidate genes, e.g., serotonin transporter, tachykinin2 (substance P), IGF 1, growth hormone and nerve growth factor beta-subunit. This and other genetic studies in progress promise to provide exciting new information on the genetics of fibromyalgia syndrome.

Presented at the National Fibromyalgia Research Association's Subgroups in Fibromyalgia Symposium, September 26-27, 1999, in Portland, Oregon.