title: A 22-single nucleotide polymorphism Alzheimer's disease risk score correlates with family history, onset age, and cerebrospinal fluid Aβ42.
abstract: BACKGROUND
  The ability to identify individuals at increased genetic risk for Alzheimer's disease (AD) may streamline biomarker and drug trials and aid clinical and personal decision making.
  
  
  METHODS
  We evaluated the discriminative ability of a genetic risk score (GRS) covering 22 published genetic risk loci for AD in 1162 Flanders-Belgian AD patients and 1019 controls and assessed correlations with family history, onset age, and cerebrospinal fluid (CSF) biomarkers (Aβ1-42, T-Tau, P-Tau181P).
  
  
  RESULTS
  A GRS including all single nucleotide polymorphisms (SNPs) and age-specific APOE ε4 weights reached area under the curve (AUC) 0.70, which increased to AUC 0.78 for patients with familial predisposition. Risk of AD increased with GRS (odds ratio, 2.32 (95% confidence interval 2.08-2.58 per unit; P < 1.0e(-15)). Onset age and CSF Aβ1-42 decreased with increasing GRS (Ponset_age = 9.0e(-11); PAβ = 8.9e(-7)).
  
  
  CONCLUSIONS
  The discriminative ability of this 22-SNP GRS is still limited, but these data illustrate that incorporation of age-specific weights improves discriminative ability. GRS-phenotype correlations highlight the feasibility of identifying individuals at highest susceptibility.
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. Electronic address: kristel.sleegers@molgen.vib-ua.be.
authors.forename: Kristel
authors.initials: K
authors.lastname: Sleegers
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Karolien
authors.initials: K
authors.lastname: Bettens
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Arne
authors.initials: A
authors.lastname: De Roeck
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Van Cauwenberghe
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Elise
authors.initials: E
authors.lastname: Cuyvers
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Verheijen
authors.affiliation: Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Hanne
authors.initials: H
authors.lastname: Struyfs
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Jasper
authors.initials: J
authors.lastname: Van Dongen
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Vermeulen
authors.affiliation: Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp Middelheim and Hoge Beuken, Antwerp, Belgium.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Engelborghs
authors.affiliation: Department of Old Age Psychiatry and Memory Clinic, University of Leuven and University Hospitals Leuven Gasthuisberg, Leuven, Belgium.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vandenbulcke
authors.affiliation: Laboratory for Cognitive Neurology, Department of Neurology, University of Leuven and University Hospitals Leuven Gasthuisberg, Leuven, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Vandenberghe
authors.affiliation: Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp Middelheim and Hoge Beuken, Antwerp, Belgium; Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: De Deyn
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. Electronic address: christine.vanbroeckhoven@molgen.vib-ua.be.
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D001530:Belgium; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D010446:Peptide Fragments; D016875:tau Proteins
keywords: Alzheimer's disease; CSF Aβ(1–42); Family history; Genetic risk profile; Genotype-phenotype correlation; Onset age