FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2028546773> ?p ?o ?g. }

• W2028546773 endingPage "117" @default.
• W2028546773 startingPage "108" @default.
• W2028546773 abstract "APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer’s Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4− (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4−: 718 cases and 1699 controls). Among APOE ɛ4− subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10−9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4− subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10−7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P⩽1.3 × 10-8), frontal cortex (P⩽1.3 × 10-9) and temporal cortex (P⩽1.2 × 10−11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10−6) and temporal cortex (P=2.6 × 10−6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ɛ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted." @default.
• W2028546773 created "2016-06-24" @default.
• W2028546773 creator A5000325789 @default.
• W2028546773 creator A5000843940 @default.
• W2028546773 creator A5000927105 @default.
• W2028546773 creator A5001196482 @default.
• W2028546773 creator A5001471706 @default.
• W2028546773 creator A5001679374 @default.
• W2028546773 creator A5001902175 @default.
• W2028546773 creator A5001995466 @default.
• W2028546773 creator A5002321122 @default.
• W2028546773 creator A5002376486 @default.
• W2028546773 creator A5002493210 @default.
• W2028546773 creator A5002505279 @default.
• W2028546773 creator A5002754020 @default.
• W2028546773 creator A5002782232 @default.
• W2028546773 creator A5002817065 @default.
• W2028546773 creator A5002821639 @default.
• W2028546773 creator A5003219679 @default.
• W2028546773 creator A5003553664 @default.
• W2028546773 creator A5003680013 @default.
• W2028546773 creator A5004141488 @default.
• W2028546773 creator A5004201320 @default.
• W2028546773 creator A5004274374 @default.
• W2028546773 creator A5004324001 @default.
• W2028546773 creator A5004390437 @default.
• W2028546773 creator A5004714044 @default.
• W2028546773 creator A5004893591 @default.
• W2028546773 creator A5004929037 @default.
• W2028546773 creator A5005004760 @default.
• W2028546773 creator A5005195577 @default.
• W2028546773 creator A5005217370 @default.
• W2028546773 creator A5005585024 @default.
• W2028546773 creator A5005674169 @default.
• W2028546773 creator A5005983470 @default.
• W2028546773 creator A5006304428 @default.
• W2028546773 creator A5006456463 @default.
• W2028546773 creator A5007160634 @default.
• W2028546773 creator A5007748241 @default.
• W2028546773 creator A5007801159 @default.
• W2028546773 creator A5008236816 @default.
• W2028546773 creator A5008405084 @default.
• W2028546773 creator A5009032548 @default.
• W2028546773 creator A5009533777 @default.
• W2028546773 creator A5009727589 @default.
• W2028546773 creator A5009834740 @default.
• W2028546773 creator A5010114260 @default.
• W2028546773 creator A5010185305 @default.
• W2028546773 creator A5010690625 @default.
• W2028546773 creator A5010807658 @default.
• W2028546773 creator A5010928244 @default.
• W2028546773 creator A5011011071 @default.
• W2028546773 creator A5011019460 @default.
• W2028546773 creator A5011198908 @default.
• W2028546773 creator A5011494296 @default.
• W2028546773 creator A5011836054 @default.
• W2028546773 creator A5011863508 @default.
• W2028546773 creator A5011932191 @default.
• W2028546773 creator A5011954398 @default.
• W2028546773 creator A5012334998 @default.
• W2028546773 creator A5012378779 @default.
• W2028546773 creator A5012540754 @default.
• W2028546773 creator A5012543104 @default.
• W2028546773 creator A5012553649 @default.
• W2028546773 creator A5012586710 @default.
• W2028546773 creator A5012810451 @default.
• W2028546773 creator A5013259227 @default.
• W2028546773 creator A5013667394 @default.
• W2028546773 creator A5013772811 @default.
• W2028546773 creator A5013907113 @default.
• W2028546773 creator A5014052615 @default.
• W2028546773 creator A5014075642 @default.
• W2028546773 creator A5014172890 @default.
• W2028546773 creator A5014216564 @default.
• W2028546773 creator A5015407411 @default.
• W2028546773 creator A5015490120 @default.
• W2028546773 creator A5015942978 @default.
• W2028546773 creator A5016023009 @default.
• W2028546773 creator A5016305380 @default.
• W2028546773 creator A5016566297 @default.
• W2028546773 creator A5016653962 @default.
• W2028546773 creator A5017009749 @default.
• W2028546773 creator A5017017613 @default.
• W2028546773 creator A5017168859 @default.
• W2028546773 creator A5017384636 @default.
• W2028546773 creator A5017437213 @default.
• W2028546773 creator A5017466982 @default.
• W2028546773 creator A5017531759 @default.
• W2028546773 creator A5017625454 @default.
• W2028546773 creator A5017902933 @default.
• W2028546773 creator A5018345023 @default.
• W2028546773 creator A5018378907 @default.
• W2028546773 creator A5018481303 @default.
• W2028546773 creator A5018633629 @default.
• W2028546773 creator A5018722034 @default.
• W2028546773 creator A5018835914 @default.
• W2028546773 creator A5018836358 @default.
• W2028546773 creator A5019253359 @default.

• next