TY - JOUR
T1 - Genetic Loci Associated with Alzheimer's Disease and Cerebrospinal Fluid Biomarkers in a Finnish Case-Control Cohort
AU - Elias-Sonnenschein, Lyzel S.
AU - Helisalmi, Seppo
AU - Natunen, Teemu
AU - Hall, Anette
AU - Paajanen, Teemu
AU - Herukka, Sanna-Kaisa
AU - Laitinen, Marjo
AU - Remes, Anne M.
AU - Koivisto, Anne M.
AU - Mattila, Kari M.
AU - Lehtimaki, Terho
AU - Verhey, Frans R. J.
AU - Visser, Pieter Jelle
AU - Soininen, Hilkka
AU - Hiltunen, Mikko
PY - 2013/4/3
Y1 - 2013/4/3
N2 - Objectives: To understand the relation between risk genes for Alzheimer's disease (AD) and their influence on biomarkers for AD, we examined the association of AD in the Finnish cohort with single nucleotide polymorphisms (SNPs) from top AlzGene loci, genome-wide association studies (GWAS), and candidate gene studies; and tested the correlation between these SNPs and AD markers A beta(1-42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). Methods: We tested 25 SNPs for genetic association with clinical AD in our cohort comprised of 890 AD patients and 701-age matched healthy controls using logistic regression. For the correlational study with biomarkers, we tested 36 SNPs in a subset of 222 AD patients with available CSF using mixed models. Statistical analyses were adjusted for age, gender and APOE status. False discovery rate for multiple testing was applied. All participants were from academic hospital and research institutions in Finland. Results: APOE-epsilon 4, CLU rs11136000, and MS4A4A rs2304933 correlated with significantly decreased A beta(1-42) (corrected p0.05). Conclusions: We provide evidence that APOE-epsilon 4, CLU and MS4A4A, which have been identified in GWAS to be associated with AD, also significantly reduced CSF A beta(1-42) in AD. None of the other AlzGene and GWAS loci showed significant effects on CSF tau. The effects of other SNPs on CSF biomarkers and clinical AD diagnosis did not reach statistical significance. Our findings suggest that APOE-epsilon 4, CLU and MS4A4A influence both AD risk and CSF A beta(1-42).
AB - Objectives: To understand the relation between risk genes for Alzheimer's disease (AD) and their influence on biomarkers for AD, we examined the association of AD in the Finnish cohort with single nucleotide polymorphisms (SNPs) from top AlzGene loci, genome-wide association studies (GWAS), and candidate gene studies; and tested the correlation between these SNPs and AD markers A beta(1-42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). Methods: We tested 25 SNPs for genetic association with clinical AD in our cohort comprised of 890 AD patients and 701-age matched healthy controls using logistic regression. For the correlational study with biomarkers, we tested 36 SNPs in a subset of 222 AD patients with available CSF using mixed models. Statistical analyses were adjusted for age, gender and APOE status. False discovery rate for multiple testing was applied. All participants were from academic hospital and research institutions in Finland. Results: APOE-epsilon 4, CLU rs11136000, and MS4A4A rs2304933 correlated with significantly decreased A beta(1-42) (corrected p0.05). Conclusions: We provide evidence that APOE-epsilon 4, CLU and MS4A4A, which have been identified in GWAS to be associated with AD, also significantly reduced CSF A beta(1-42) in AD. None of the other AlzGene and GWAS loci showed significant effects on CSF tau. The effects of other SNPs on CSF biomarkers and clinical AD diagnosis did not reach statistical significance. Our findings suggest that APOE-epsilon 4, CLU and MS4A4A influence both AD risk and CSF A beta(1-42).
U2 - 10.1371/journal.pone.0059676
DO - 10.1371/journal.pone.0059676
M3 - Article
C2 - 23573206
SN - 1932-6203
VL - 8
JO - PLOS ONE
JF - PLOS ONE
IS - 4
M1 - e59676
ER -