Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample

Rosa Rademakers, Marc Cruts, Kristel Sleegers, Bart Dermaut, Jessie Theuns, Yurii Aulchenko, Stefan Weckx, Tim De Pooter, Marleen Van Den Broeck, Ellen Corsmit, Peter De Rijk, Jurgen Del-Favero, John Van Swieten, Cornelia M. Van Duijn, Christine Van Broeckhoven

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


We obtained conclusive linkage of Alzheimer disease (AD) with a candidate region of 19.7 cM at 7q36 in an extended multiplex family, family 1270, ascertained in a population-based study of early-onset AD in the northern Netherlands. Single-nucleotide polymorphism and haplotype association analyses of a Dutch patient-control sample further supported the linkage at 7q36. In addition, we identified a shared haplotype at 7q36 between family 1270 and three of six multiplex AD-affected families from the same geographical region, which is indicative of a founder effect and defines a priority region of 9.3 cM. Mutation analysis of coding exons of 29 candidate genes identified one linked synonymous mutation, g.38030G→C in exon 10, that affected codon 626 of the PAX transactivation domain interacting protein gene (PAXIP1). It remains to be determined whether PAXIP1 has a functional role in the expression of AD in family 1270 or whether another mutation at this locus explains the observed linkage and sharing. Together, our linkage data from the informative family 1270 and the association data in the population-based early-onset AD patient-control sample strongly support the identification of a novel AD locus at 7q36 and re-emphasize the genetic heterogeneity of AD.

Original languageEnglish (US)
Pages (from-to)643-652
Number of pages10
JournalAmerican journal of human genetics
Issue number4
StatePublished - Oct 2005

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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