Comprehensive Search for Alzheimer Disease Susceptibility Loci in the APOE Region

SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

“…This conclusion is consistent with the observation of moderate linkage disequilibrium between the SNPs determining APOE genotype, rs7412 and rs429358 (Fig. S5), SNPs showing genomewide significant evidence for association with LOAD without adjustment for APOE genotype, and our prior LOAD association studies with SNPs in this region among Caucasians [13].…”

“…Association of AD with this SNP, which is located approximately 225 kb from APOE , has not been observed previously. PVRL2 and APOE are located in a genomic region sandwiched between two recombination hotspots [26], where strong association signals for LOAD have been reproducibly detected in Caucasians [1], [5], but dissipate almost completely for all non- APOE loci after conditioning on APOE , suggesting that no other loci in this region influence LOAD susceptibility [13]. This conclusion is consistent with the observation of moderate linkage disequilibrium between the SNPs determining APOE genotype, rs7412 and rs429358 (Fig.…”

SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

“…This conclusion is consistent with the observation of moderate linkage disequilibrium between the SNPs determining APOE genotype, rs7412 and rs429358 (Fig. S5), SNPs showing genomewide significant evidence for association with LOAD without adjustment for APOE genotype, and our prior LOAD association studies with SNPs in this region among Caucasians [13].…”

“…Association of AD with this SNP, which is located approximately 225 kb from APOE , has not been observed previously. PVRL2 and APOE are located in a genomic region sandwiched between two recombination hotspots [26], where strong association signals for LOAD have been reproducibly detected in Caucasians [1], [5], but dissipate almost completely for all non- APOE loci after conditioning on APOE , suggesting that no other loci in this region influence LOAD susceptibility [13]. This conclusion is consistent with the observation of moderate linkage disequilibrium between the SNPs determining APOE genotype, rs7412 and rs429358 (Fig.…”

Transethnic genome‐wide scan identifies novel Alzheimer's disease loci

“…A total of 35 SNPs from nine novel loci met criteria for follow up in Stage 2 ( Supplementary Table 3 ). Extensive evaluation of SNPs from the APOE region across the different ethnic groups demonstrated that only the APOE ε2 SNP (rs7412) remained genome-wide significant among APOE ε4− subjects ( Supplementary Table 4 ), confirming our prior observation that APOE accounts for all association signals in this region [22]. SNPs in other loci showed suggestive evidence for association (P<10 −6 ) in EAs or AAs ( Supplementary Table 5 ), but these results were much less significant in the transethnic meta-analyses.…”

A candidate gene study of risk for dementia in older, postmenopausal women: Results from the Women's Health Initiative Memory Study

“…Our results in older women are in line with and provide additional support for a role of APOE/TOMM40 in dementia risk . A comprehensive search for AD susceptibility loci in the APOE region suggests that APOE alleles could essentially account for all the inherited AD risk and that other variants, including poly‐T‐track in TOMM40 , do not seem to pose independent risks . In our sample, the results remained largely unchanged when A POE SNPs that define epsilon 2/3/4 genotypes were added to the analyses as covariates.…”

SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

“…This conclusion is consistent with the observation of moderate linkage disequilibrium between the SNPs determining APOE genotype, rs7412 and rs429358 (Fig. S5), SNPs showing genomewide significant evidence for association with LOAD without adjustment for APOE genotype, and our prior LOAD association studies with SNPs in this region among Caucasians [13].…”

“…Association of AD with this SNP, which is located approximately 225 kb from APOE , has not been observed previously. PVRL2 and APOE are located in a genomic region sandwiched between two recombination hotspots [26], where strong association signals for LOAD have been reproducibly detected in Caucasians [1], [5], but dissipate almost completely for all non- APOE loci after conditioning on APOE , suggesting that no other loci in this region influence LOAD susceptibility [13]. This conclusion is consistent with the observation of moderate linkage disequilibrium between the SNPs determining APOE genotype, rs7412 and rs429358 (Fig.…”

Transethnic genome‐wide scan identifies novel Alzheimer's disease loci

“…A total of 35 SNPs from nine novel loci met criteria for follow up in Stage 2 ( Supplementary Table 3 ). Extensive evaluation of SNPs from the APOE region across the different ethnic groups demonstrated that only the APOE ε2 SNP (rs7412) remained genome-wide significant among APOE ε4− subjects ( Supplementary Table 4 ), confirming our prior observation that APOE accounts for all association signals in this region [22]. SNPs in other loci showed suggestive evidence for association (P<10 −6 ) in EAs or AAs ( Supplementary Table 5 ), but these results were much less significant in the transethnic meta-analyses.…”

A candidate gene study of risk for dementia in older, postmenopausal women: Results from the Women's Health Initiative Memory Study

“…Our results in older women are in line with and provide additional support for a role of APOE/TOMM40 in dementia risk . A comprehensive search for AD susceptibility loci in the APOE region suggests that APOE alleles could essentially account for all the inherited AD risk and that other variants, including poly‐T‐track in TOMM40 , do not seem to pose independent risks . In our sample, the results remained largely unchanged when A POE SNPs that define epsilon 2/3/4 genotypes were added to the analyses as covariates.…”

SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

“…This conclusion is consistent with the observation of moderate linkage disequilibrium between the SNPs determining APOE genotype, rs7412 and rs429358 (Fig. S5), SNPs showing genomewide significant evidence for association with LOAD without adjustment for APOE genotype, and our prior LOAD association studies with SNPs in this region among Caucasians [13].…”

“…Association of AD with this SNP, which is located approximately 225 kb from APOE , has not been observed previously. PVRL2 and APOE are located in a genomic region sandwiched between two recombination hotspots [26], where strong association signals for LOAD have been reproducibly detected in Caucasians [1], [5], but dissipate almost completely for all non- APOE loci after conditioning on APOE , suggesting that no other loci in this region influence LOAD susceptibility [13]. This conclusion is consistent with the observation of moderate linkage disequilibrium between the SNPs determining APOE genotype, rs7412 and rs429358 (Fig.…”

Transethnic genome‐wide scan identifies novel Alzheimer's disease loci

“…A total of 35 SNPs from nine novel loci met criteria for follow up in Stage 2 ( Supplementary Table 3 ). Extensive evaluation of SNPs from the APOE region across the different ethnic groups demonstrated that only the APOE ε2 SNP (rs7412) remained genome-wide significant among APOE ε4− subjects ( Supplementary Table 4 ), confirming our prior observation that APOE accounts for all association signals in this region [22]. SNPs in other loci showed suggestive evidence for association (P<10 −6 ) in EAs or AAs ( Supplementary Table 5 ), but these results were much less significant in the transethnic meta-analyses.…”

A candidate gene study of risk for dementia in older, postmenopausal women: Results from the Women's Health Initiative Memory Study

“…Our results in older women are in line with and provide additional support for a role of APOE/TOMM40 in dementia risk . A comprehensive search for AD susceptibility loci in the APOE region suggests that APOE alleles could essentially account for all the inherited AD risk and that other variants, including poly‐T‐track in TOMM40 , do not seem to pose independent risks . In our sample, the results remained largely unchanged when A POE SNPs that define epsilon 2/3/4 genotypes were added to the analyses as covariates.…”