Assessment of Alzheimer's disease case-control associations using family-based methods - PubMed (original) (raw)

Assessment of Alzheimer's disease case-control associations using family-based methods

Brit-Maren M Schjeide et al. Neurogenetics. 2009 Feb.

Abstract

The genetics of Alzheimer's disease (AD) is heterogeneous and remains only ill-defined. We have recently created a freely available and continuously updated online database (AlzGene; http://www.alzgene.org ) for which we collect all published genetic association studies in AD and perform systematic meta-analyses on all polymorphisms with sufficient genotype data. In this study, we tested 27 genes (ACE, BDNF, CH25H, CHRNB2, CST3, CTSD, DAPK1, GALP, hCG2039140, IL1B, LMNA, LOC439999, LOC651924, MAPT, MTHFR, MYH13, PCK1, PGBD1, PRNP, PSEN1, SORCS1, SORL1, TF, TFAM, TNK1, GWA_14q32.13, and GWA_7p15.2), all showing significant association with AD risk in the AlzGene meta-analyses, in a large collection of family-based samples comprised of 4,180 subjects from over 1,300 pedigrees. Overall, we observe significant association with risk for AD and polymorphisms in ACE, CHRNB2, TF, and an as yet uncharacterized locus on chromosome 7p15.2 [rs1859849]. For all four loci, the association was observed with the same alleles as in the AlzGene meta-analyses. The convergence of case-control and family-based findings suggests that these loci currently represent the most promising AD gene candidates. Further fine-mapping and functional analyses are warranted to elucidate the potential biochemical mechanisms and epidemiological relevance of these genes.

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References

    1. Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet. 2007;39:17–23. doi: 10.1038/ng1934. - DOI - PubMed
    1. Bertram L, Blacker D, Crystal A, Mullin K, Keeney D, Jones J, et al. Candidate genes showing no evidence for association or linkage with Alzheimer’s disease using family-based methodologies. Exp Gerontol. 2000;35:1353–1361. doi: 10.1016/S0531-5565(00) 00193-5. - DOI - PubMed
    1. Rogaeva E, Meng Y, Lee JH, Gu Y, Kawarai T, Zou F, et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet. 2007;39:168–177. doi: 10.1038/ng1943. - DOI - PMC - PubMed
    1. Laird NM, Lange C. Family-based designs in the age of large-scale gene-association studies. Nat Rev Genet. 2006;7:385–394. doi: 10.1038/nrg1839. - DOI - PubMed
    1. Blacker D, Haines JL, Rodes L, Terwedow H, Go RC, Harrell LE, et al. ApoE-4 and age at onset of Alzheimer’s disease: the NIMH genetics initiative. Neurology. 1997;48:139–147. - PubMed

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