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Besides considering the most significant variants, we also tried to relax the significance threshold, allowing more markers to be fitted.
The three most significant variants, rs12668955, rs1006417 and rs147564881 were selected and genotyped in a Swedish CH case-control study population.
Firstly, we focus on the comparison of using only the most significant variants passing Bonferroni correction versus using all variants below a certain local fdr threshold.
The most significant variants in the regions were the rs864745 in intron 1 of JAZF1, rs12779790 between CDC123 and CAMK1D, rs7961581 between TSPAN8 and LGR5, rs7578597 in exon 24 of THADA, rs4607103 near ADAMTS9 and rs10923931 in intron 5 of NOTCH2 [6].
Interestingly, bioinformatic analysis of the top 10 most significant variants located in untranslated regions revealed SNPs located in the 5' UTR of IGFBP5, MAPK9 and GCK were predicted to collectively modulate 11 transcription factor binding sites (TFBS) and SNPs in the 3' UTR of HK1, SLC2A1 and ESR2 were predicted to modulate six miRNA binding sites.
Here we evaluate in our large case control series (n = 5,043) the most significant variants in TNK1, GAB2, LOC651924, GWA_14q32.13, PGBD1 and GALP for genetic association with LOAD, as well as nine previously suggested candidate LOAD genes (Grupe et al. 2007).
Similar(54)
These variants are mostly associated with intronic and intergenic regions, with the most significant variant regulating the level of gene expression of FGFR2 [ 6].
Thus the length of introns is the most significant variant that contributes to the difference in the gene size between the groups.
The independent association signals in regions with multiple associations were defined using stepwise logistic regression conditioning on the most significant variant.
The process is usually repeated with the next most significant variant and so forth until all remaining association in the locus can be accounted for.
In general, by applying this method, the most significant variant in overlapping LD blocks were considered as the true association of a gene.
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