[PROVISIONAL] The combined risk effect among BIN1, CLU and APOE genes in Alzheimer’s disease

• Published in: Genetics and Molecular Biology
• Main Authors: Lígia Ramos dos Santos, Jucimara Ferreira Figueiredo Almeida, Lúcia Helena Sagrillo Pimassoni, Renato Lírio Morelato, Flavia de Paula
• Format: Article
• Language: English
• Published: Sociedade Brasileira de Genética
• Subjects: GWAS variants; APOE; CLU; BIN1; ABCA7
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019005040102&lng=en&tlng=en

Abstract Genome-wide associations studies (GWAS) have been detecting new variants associated with late-onset of Alzheimer’s disease (LOAD), a multifactorial neurodegenerative disorder. The variants rs744373 BIN1, rs11136000 CLU rs3764650 ABCA7 uncovered by GWAS led to different AD pathways, such as metabolism, trafficking and endocytosis of lipids and inflammation. However, most of the association studies did not replicate these variants with significance. This could be due to a small power effect evident when these variants are tested independently with LOAD. Therefore, we aimed to investigate if the combination of different variants would additively modify the risk of association with LOAD that is observed in GWAS. We performed an association study testing pairwise variants in metabolism, trafficking and endocytosis of lipid (rs429358 and rs7412 APOE, rs744373 BIN1, rs3764650 ABCA7 and rs11136000 CLU) pathways with LOAD in samples from southeastern Brazil. Our data suggest a risk effect for LOAD between APOE with CLU and APOE with BIN1 genes.