**3. Population-based association for ALS and FTLD to chromosome 9p**

In 2009, the first ALS GWAS showing association with a locus at chromosome 9p21 was reported by Van Es and colleagues. They identified genome-wide significance with two SNPs, rs2814707 and rs3849942, almost in complete linkage disequilibrium (LD) with each other and located in an LD block of ~80 kb. Also a third SNP in this LD block (rs774359) showed suggestive association (figure 1). This LD block is situated at the telomeric end of the minimally linked candidate region found in the ALS-FTLD families and contains only three genes: part of *MOBKL2B*, *IFNK* and *C9orf72* (figure 1). Next, data of the first GWAS in FTLD-TDP were suggestive for association of five SNPs (rs774352, rs774351, rs3849942, rs2814707, rs774359) on chromosome 9p21, in the same LD block (Van Deerlin et al., 2010). Subsequently, a Finnish and a British independent ALS GWAS identified genome-wide significance with SNPs rs3849942, rs2814707, rs774359, rs2225389 (Laaksovirta et al., 2010) and with SNPs rs3849942, rs2814707, rs903603 (Shatunov et al., 2010) respectively, all in the same locus at chromosome 9p21. The Finnish study defined a 42-SNP haplotype associated with increased risk of ALS in the Finnish population, located in a 232 kb LD block which overlaps with the previously reported 80 kb LD block (van Es et al., 2009) and the 106.5 kb LD block of the UK study (Shatunov et al., 2010). Because of the unique homogeneous genetic structure of the Finnish isolated population, the extent and structure of LD is different than in other European countries. To date, one study replicated the association of the chr9p21 locus in an ALS-FTLD subpopulation (Rollinson et al., 2011).

To assess the contribution of the chr9p21 risk factor to disease etiology in Belgium, we replicated one of the top SNPs associated in all GWAS reports, rs2814707, in a Belgian population of ALS, ALS-FTLD and FTLD patients. In addition, we performed a metaanalysis of the different published association studies with inclusion of our study.
