title: Linkage analysis of autopsy-confirmed familial Alzheimer disease supports an Alzheimer disease locus in 8q24.
abstract: OBJECTIVE
  We have previously reported the results of an extended genome-wide scan of Swedish Alzheimer disease (AD)-affected families; in this paper, we analyzed a subset of these families with autopsy-confirmed AD.
  
  
  METHODS
  We report the fine-mapping, using both microsatellite markers and single-nucleotide polymorphisms (SNPs), in the observed maximum logarithm of the odds (LOD)-2 unit (LOD(max)-2) region under the identified linkage peak, linkage analysis of the fine-mapping data with additionally analyzed pedigrees, and association analysis of SNPs selected from candidate genes in the linked interval. The subset was made on the criterion of at least one autopsy-confirmed AD case per family, resulting in 24 families.
  
  
  RESULTS
  Linkage analysis of a family subset having at least one autopsy-confirmed AD case showed a significant nonparametric single-point LOD score of 4.4 in 8q24. Fine-mapping under the linkage peak with 10 microsatellite markers yielded an increase in the multipoint (mpt) LOD score from 2.1 to 3.0. SNP genotyping was performed on 21 selected candidate transcripts of the LOD(max)-2 region. Both family-based association and linkage analysis were performed on extended material from 30 families, resulting in a suggestive linkage at peak marker rs6577853 (mpt LOD score = 2.4).
  
  
  CONCLUSIONS
  The 8q24 region has been implicated to be involved in AD etiology.
authors.affiliation: Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, KI-ADRC, KASPAC, Novum, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Sillén
authors.forename: Jesper
authors.initials: J
authors.lastname: Brohede
authors.forename: Charlotte
authors.initials: C
authors.lastname: Forsell
authors.forename: Lena
authors.initials: L
authors.lastname: Lilius
authors.forename: Jorge
authors.initials: J
authors.lastname: Andrade
authors.forename: Jacob
authors.initials: J
authors.lastname: Odeberg
authors.forename: Toru
authors.initials: T
authors.lastname: Kimura
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D001344:Autopsy; D001921:Brain / Q000473:pathology; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013548:Sweden / Q000453:epidemiology
chemical_list: D004247:DNA