Linkage to 20p13 including the ANGPT4 gene in families with mixed Alzheimer's disease and vascular dementia

• Published in: Journal of human genetics Vol. 55; no. 10; pp. 649 - 655
• Main Authors: Sillén, Anna, Brohede, Jesper, Lilius, Lena, Forsell, Charlotte, Andrade, Jorge, Odeberg, Jacob, Ebise, Hayao, Winblad, Bengt, Graff, Caroline
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.10.2010
• Subjects: Alzheimer Disease - genetics; Alzheimer's disease; Angiogenesis; Angiopoietins - genetics; ANGPT4; association study; Bioengineering; Bioteknik; candidate genes; Chromosome Mapping; Chromosomes, Human, Pair 20; Dementia; Dementia disorders; Dementia, Vascular - genetics; familial dementia; Family Health; Female; Gene mapping; Genomes; Humans; linkage analysis; Lod Score; Male; Medicin och hälsovetenskap; Microsatellite Repeats; Microsatellites; Neurodegenerative diseases; Phenotype; Phenotypes; Physical Chromosome Mapping; Polymorphism, Single Nucleotide; Single-nucleotide polymorphism; SNP; TECHNOLOGY; TEKNIKVETENSKAP; Vascular dementia; Vascular diseases
• ISSN: 1434-5161; 1435-232X; 1435-232X
• DOI: 10.1038/jhg.2010.79

This study aimed at identifying novel susceptibility genes for a mixed phenotype of Alzheimer's disease and vascular dementia. Results from a genome scan showed strongest linkage to 20p13 in 18 families, and subsequent fine mapping was performed with both microsatellites and single-nucleotide polymorphisms in 18 selected candidate transcripts in an extended sample set of 30 families. The multipoint linkage peak was located at marker rs2144151 in the ANGPT4 gene, which is a strong candidate gene for vascular disease because of its involvement in angiogenesis. Although the significance of the linkage decreased, we find this result intriguing, considering that we included additional families, and thus the reduced linkage signal may be caused by genetic heterogeneity.