@article {7786, title = {Genetic Variation in Genes Underlying Diverse Dementias May Explain a Small Proportion of Cases in the Alzheimer{\textquoteright}s Disease Sequencing Project.}, journal = {Dement Geriatr Cogn Disord}, volume = {45}, year = {2018}, month = {2018}, pages = {1-17}, abstract = {

BACKGROUND/AIMS: The Alzheimer{\textquoteright}s Disease Sequencing Project (ADSP) aims to identify novel genes influencing Alzheimer{\textquoteright}s disease (AD). Variants within genes known to cause dementias other than AD have previously been associated with AD risk. We describe evidence of co-segregation and associations between variants in dementia genes and clinically diagnosed AD within the ADSP.

METHODS: We summarize the properties of known pathogenic variants within dementia genes, describe the co-segregation of variants annotated as "pathogenic" in ClinVar and new candidates observed in ADSP families, and test for associations between rare variants in dementia genes in the ADSP case-control study. The participants were clinically evaluated for AD, and they represent European, Caribbean Hispanic, and isolate Dutch populations.

RESULTS/CONCLUSIONS: Pathogenic variants in dementia genes were predominantly rare and conserved coding changes. Pathogenic variants within ARSA, CSF1R, and GRN were observed, and candidate variants in GRN and CHMP2B were nominated in ADSP families. An independent case-control study provided evidence of an association between variants in TREM2, APOE, ARSA, CSF1R, PSEN1, and MAPT and risk of AD. Variants in genes which cause dementing disorders may influence the clinical diagnosis of AD in a small proportion of cases within the ADSP.

}, issn = {1421-9824}, doi = {10.1159/000485503}, author = {Blue, Elizabeth E and Bis, Joshua C and Dorschner, Michael O and Tsuang, Debby W and Barral, Sandra M and Beecham, Gary and Below, Jennifer E and Bush, William S and Butkiewicz, Mariusz and Cruchaga, Carlos and DeStefano, Anita and Farrer, Lindsay A and Goate, Alison and Haines, Jonathan and Jaworski, Jim and Jun, Gyungah and Kunkle, Brian and Kuzma, Amanda and Lee, Jenny J and Lunetta, Kathryn L and Ma, Yiyi and Martin, Eden and Naj, Adam and Nato, Alejandro Q and Navas, Patrick and Nguyen, Hiep and Reitz, Christiane and Reyes, Dolly and Salerno, William and Schellenberg, Gerard D and Seshadri, Sudha and Sohi, Harkirat and Thornton, Timothy A and Valadares, Otto and van Duijn, Cornelia and Vardarajan, Badri N and Wang, Li-San and Boerwinkle, Eric and Dupuis, Jos{\'e}e and Pericak-Vance, Margaret A and Mayeux, Richard and Wijsman, Ellen M} }