title: A study of the SORL1 gene in Alzheimer's disease and cognitive function.
abstract: Several studies have investigated the role of the neuronal sortilin-related receptor (SORL1) gene in Alzheimer's disease (AD), but findings have been inconsistent. We conducted a study of 7 single nucleotide polymorphisms (SNPs), rs668387, rs689021, rs641120, rs1699102, rs3824968, rs2282649, and rs1010159, in the SORL1 gene that were associated to AD in previous studies. We tested for association with AD and cognitive function in 6741 participants of the Rotterdam Study and in 2883 individuals from the Erasmus Rucphen Family study. We performed meta-analyses on AD using our data together with those of previous studies published prior to September 2008 in Caucasians. Further, we studied up to 76 SNPs in a 400 kb region within and flanking the gene to evaluate the evidence that other genetic variants are associated with AD or cognitive function. There was no significant evidence for association between SORL1 SNPs and incident AD patients in the Rotterdam Study. In a meta-analysis of our data with those of others, six out of seven SNPs attained borderline significance. However, removal of the first study reporting association from the meta-analysis resulted in non-significant odds ratios for all SNPs. SNPs rs668387, rs689021, and rs641120 were associated with cognitive function in non-demented individuals at borderline statistical significance in two independent Dutch cohorts, but in the opposite direction. Testing for association using dense SNPs in the SORL1 gene did not reveal significant association with AD, or with cognitive function when adjusting for multiple testing. In conclusion, our data do not support the hypothesis that genetic variants in SORL1 are related to the risk of AD.
authors: Genetic Epidemiology Unit, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Fan
authors: F
authors: Liu
authors: M Arfan
authors: MA
authors: Ikram
authors: A Cecile J W
authors: AC
authors: Janssens
authors: Maaike
authors: M
authors: Schuur
authors: Inge
authors: I
authors: de Koning
authors: Aaron
authors: A
authors: Isaacs
authors: Maksim
authors: M
authors: Struchalin
authors: Andre G
authors: AG
authors: Uitterlinden
authors: Johan T
authors: JT
authors: den Dunnen
authors: Kristel
authors: K
authors: Sleegers
authors: Karolien
authors: K
authors: Bettens
authors: Christine
authors: C
authors: Van Broeckhoven
authors: John
authors: J
authors: van Swieten
authors: Albert
authors: A
authors: Hofman
authors: Ben A
authors: BA
authors: Oostra
authors: Yurii S
authors: YS
authors: Aulchenko
authors: Monique M B
authors: MM
authors: Breteler
authors: Cornelia M
authors: CM
authors: van Duijn
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D003071:Cognition / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics* / Q000502:physiology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C102582:SORL1 protein, human