TY - JOUR T1 - Significant linkage to chromosome 12q24.32–q24.33 and identification of <em>SFRS8</em> as a possible asthma susceptibility gene JF - Thorax JO - Thorax SP - 874 LP - 879 DO - 10.1136/thx.2005.055475 VL - 61 IS - 10 AU - C Brasch-Andersen AU - Q Tan AU - A D Børglum AU - A Haagerup AU - T R Larsen AU - J Vestbo AU - T A Kruse Y1 - 2006/10/01 UR - http://thorax.bmj.com/content/61/10/874.abstract N2 - Background: Asthma is a complex genetic disorder. Many studies have suggested that chromosome 12q harbours a susceptibility gene for asthma and atopy. Linkage on chromosome 12q24.21–q24.33 was investigated in 167 Danish families with asthma.Methods: A two step procedure was used: (1) a genome-wide scan in one set of families followed by (2) fine scale mapping in an independent set of families in candidate regions with a maximum likelihood score (MLS) of ⩾1.5 in the genome-wide scan. Polymorphisms in a candidate gene in the region on 12q24.33 were tested for association with asthma in a family based transmission disequilibrium test.Results: An MLS of 3.27 was obtained at 12q24.33. The significance of this result was tested by simulation, resulting in a significant empirical genome-wide p value of 0.018. To our Knowledge, this is the first significant evidence for linkage on chromosome 12q, and suggests a candidate region distal to most previously reported regions. Three single nucleotide polymorphisms in splicing factor, arginine/serine-rich 8 (SFRS8) had an association with asthma (p⩽0.0020–0.050) in a sample of 136 asthmatic sib pairs. SFRS8 regulates the splicing of CD45, a protein which, through alternative splice variants, has an essential role in activating T cells. T cells are involved in the pathogenesis of atopic diseases such as asthma, so SFRS8 is a very interesting candidate gene in the region.Conclusions: Linkage and simulation studies show that the very distal part of chromosome 12q contains a gene that increases the susceptibility to asthma. SFRS8 could act as a weak predisposing gene for asthma in our sample. ER -