%0 Journal Article %1 li2006dapk1expression. %A Li, Y %A Grupe, A %A Rowland, C %A Nowotny, P %A Kauwe, JS %A Smemo, S %A Hinrichs, A %A Tacey, K %A Toombs, TA %A Kwok, S %A Catanese, J %A White, TJ %A Maxwell, TJ %A Hollingworth, P %A Abraham, R %A Rubinsztein, DC %A Brayne, C %A Wavrant-De Vrièze, F %A Hardy, J %A O'Donovan, M %A Lovestone, S %A Morris, JC %A Thal, LJ %A Owen, M %A Williams, J %A Goate, A %C Celera Diagnostics, Alameda, CA 94502, USA. yonghong.li@celeradiagnostics.com %D 2006 %J Hum Mol Genet %K imported %N 17 %P 2560--2568 %R 10.1093/hmg/ddl178 %T DAPK1 variants are associated with Alzheimer's disease and allele-specific expression. %U http://www.ncbi.nlm.nih.gov/pubmed/16847012 %V 15 %X Genetic factors play an important role in the etiology of late-onset Alzheimer's disease (LOAD). We tested gene-centric single nucleotide polymorphisms (SNPs) on chromosome 9 and identified two SNPs in the death-associated protein kinase, DAPK1, that show significant association with LOAD. SNP rs4878104 was significantly associated with LOAD in our discovery case-control sample set (WU) and replicated in each of two initial validation case-control sample sets (P<0.05, UK1, SD). The risk-allele frequency of this SNP showed a similar direction in three other case-control sample sets. A meta-analysis of the six sample sets combined, totaling 2012 cases and 2336 controls, showed an allelic P-value of 0.0016 and an odds ratio (OR) of 0.87 (95%CI: 0.79-0.95). Minor allele homozygotes had a consistently lower risk than major allele homozygotes in the discovery and initial two replication sample sets, which remained significant in the meta-analysis of all six sample sets (OR=0.7, 95%CI: 0.58-0.85), whereas the risk for heterozygous subjects was not significantly different from that of major allele homozygotes. A second SNP, rs4877365, which is in high linkage disequilibrium with rs4878104 (r2=0.64), was also significantly associated with LOAD (meta P=0.0017 in the initial three sample sets). Furthermore, DAPK1 transcripts show differential allelic gene expression, and both rs4878104 and rs4877365 were significantly associated with DAPK1 allele-specific expression (P=0.015 to <0.0001). These data suggest that genetic variation in DAPK1 modulates susceptibility to LOAD.

@article{li2006dapk1expression., abstract = {Genetic factors play an important role in the etiology of late-onset Alzheimer's disease (LOAD). We tested gene-centric single nucleotide polymorphisms (SNPs) on chromosome 9 and identified two SNPs in the death-associated protein kinase, DAPK1, that show significant association with LOAD. SNP rs4878104 was significantly associated with LOAD in our discovery case-control sample set (WU) and replicated in each of two initial validation case-control sample sets (P<0.05, UK1, SD). The risk-allele frequency of this SNP showed a similar direction in three other case-control sample sets. A meta-analysis of the six sample sets combined, totaling 2012 cases and 2336 controls, showed an allelic P-value of 0.0016 and an odds ratio (OR) of 0.87 (95%CI: 0.79-0.95). Minor allele homozygotes had a consistently lower risk than major allele homozygotes in the discovery and initial two replication sample sets, which remained significant in the meta-analysis of all six sample sets (OR=0.7, 95%CI: 0.58-0.85), whereas the risk for heterozygous subjects was not significantly different from that of major allele homozygotes. A second SNP, rs4877365, which is in high linkage disequilibrium with rs4878104 (r2=0.64), was also significantly associated with LOAD (meta P=0.0017 in the initial three sample sets). Furthermore, DAPK1 transcripts show differential allelic gene expression, and both rs4878104 and rs4877365 were significantly associated with DAPK1 allele-specific expression (P=0.015 to <0.0001). These data suggest that genetic variation in DAPK1 modulates susceptibility to LOAD.}, added-at = {2013-08-12T12:53:15.000+0200}, address = {Celera Diagnostics, Alameda, CA 94502, USA. yonghong.li@celeradiagnostics.com}, author = {Li, Y and Grupe, A and Rowland, C and Nowotny, P and Kauwe, JS and Smemo, S and Hinrichs, A and Tacey, K and Toombs, TA and Kwok, S and Catanese, J and White, TJ and Maxwell, TJ and Hollingworth, P and Abraham, R and Rubinsztein, DC and Brayne, C and Wavrant-De Vrièze, F and Hardy, J and O'Donovan, M and Lovestone, S and Morris, JC and Thal, LJ and Owen, M and Williams, J and Goate, A}, biburl = {https://www.bibsonomy.org/bibtex/256f6afd8d632e9d16f3427c36b91d7e3/sokratesagogo}, day = 1, doi = {10.1093/hmg/ddl178}, interhash = {bd5b310d3f0858bf366e09e2f6431813}, intrahash = {56f6afd8d632e9d16f3427c36b91d7e3}, issn = {0964-6906}, journal = {Hum Mol Genet}, keyword = {Alleles}, keywords = {imported}, language = {eng}, month = Sep, number = 17, organization = {England}, pages = {2560--2568}, pii = {ddl178}, timestamp = {2013-08-12T12:53:42.000+0200}, title = {DAPK1 variants are associated with Alzheimer's disease and allele-specific expression.}, url = {http://www.ncbi.nlm.nih.gov/pubmed/16847012}, volume = 15, year = 2006 }