The previous genome-wide scan in Scandinavian families supported earlier evidence for linkage of a region on chromosome 5 (5q31-33) to coeliac disease. This study deals with further genetic mapping of an 18 cM region, spanning from marker GAh18A (131.87 Mb) to D5S640 (149.96 Mb). Linkage and association analyses were performed in a two-step approach. First, seven microsatellites were added. Strong evidence for linkage was obtained with a Zlr score of 3.96, P(nc) = 4 x 10(-5) at marker D5S436. The strongest association was with a haplotype consisting of the markers D5S2033 and D5S2490 (P(nc) < 0.001). In the second step, we added 17 microsatellites and 69 single nucleotide polymorphisms (SNPs) to the analysis. These markers were located close to or within candidate genes across the region of approximately 7 Mb beneath the linkage peak marked by D5S2017 and D5S812. A substantial increase of the linkage signal with a maximum Zlr score of 4.6 at marker rs1972644 (P(nc) = 2 x 10(-6)) was obtained and several SNPs showed association. Seven SNPs that individually showed the strongest association were genotyped in a second independent family sample set (225 trios). In the trio family sample as well as in the multiplex family sample, the strongest association was found with SNPs within the region flanked by the associated microsatellites D5S2033 and D5S2490 at 5q32.

The importance of pubertal timing for adult BMD in males was studied through association of pubertal timing with young adult bone phenotype. Pubertal timing was found to predict both cortical and trabecular volumetric BMD and previous fractures in young adult men. Thus, late puberty is a risk factor for low BMD and previous fractures in young adult men.