A two‐stage, genome‐wide screen for susceptibility loci in primary Raynaud's phenomenon

Objective To identify chromosomal regions containing genes involved in the susceptibility to primary Raynaud's phenomenon (RP). Methods Six extended families with multiple individuals affected with primary RP (n = 37) were examined for linkage in a 2‐stage, whole‐genome screen, using a total of 298 microsatellite markers. Results Multipoint, nonparametric linkage analysis identified 5 areas of possible linkage, with a nominal level of significance of P ≤ 0.05. Analysis of a finer map of markers in these regions defined the regions of linkage as 21.4 cM on 6q13–6q23.3 (D6S261; P = 0.0004), 10.2 cM on 7p22–7p15 (D7S664; P = 0.014), 1.6 cM on 9p23–9p22 (D9S156; P = 0.0075), 5.1 cM on 17p13.1–17p12 (D17S1791; P = 0.036), and 11.8 cM on Xp11.4–Xp11.23 (DXS8054; P = 0.006). Three potential candidate genes map to these regions: the β subunit of the muscle acetylcholine receptor and the serotonin 1B and 1E receptors. Conclusion These results provide evidence of the presence and location of genes that are involved in the genetic susceptibility to primary RP.