Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

• Published in: Nature genetics Vol. 49; no. 9; pp. 1373 - 1384
• Main Authors: Badarinarayan, Nandini, Bis, Joshua C, Heilmann-Heimbach, Stefanie, Sleegers, Kristel, Vronskaya, Maria, White, Charles C, Hamilton-Nelson, Kara L, Choi, Seung-Hoan, Forstner, Andreas J, Bacq, Delphine, Brody, Jennifer A, Wolters, Frank J, Fornage, Myriam, Majounie, Elisa, Wallon, David, Lupton, Michelle K, Jian, Xueqiu, Mukherjee, Shubhabrata, Solfrizzi, Vincenzo, Allen, Mariet, Cupples, L Adrienne, Giegling, Ina, Giedraitis, Vilmantas, Wang, Xue, Mecocci, Patrizia, Eiriksdottir, Gudny, Chen, Yuning, Frosch, Matthew P, Huebinger, Ryan M, Morris, John, Sotolongo-Grau, Oscar, Katz, Mindy J, Braddel, Amy, Chapman, Jade, Hill, Matt, Vellas, Bruno, Soininen, Hilkka, Hughes, Joseph T, Mayhaus, Manuel, Maletta, Raffaele Giovanni, Carrell, David, Pilotto, Alberto, Fox, Nick C, Arnold, Steven E, Becker, James T, Burke, James R, Carlsson, Cynthia M, Clark, David G, Cribbs, David H, Duara, Ranjan, Evans, Denis A, Fallon, Kenneth B, Farlow, Martin R, Foroud, Tatiana M, Galasko, Douglas R, Jin, Lee-Way, Lah, James J, Levey, Allan I, Lieberman, Andrew P, McKee, Ann C, Morris, John C, Paulson, Henry L, Peskind, Elaine, Quinn, Joseph F, Raskind, Murray, Spina, Salvatore, Swerdlow, Russell H, Van Eldik, Linda J, Vinters, Harry V, Vonsattel, Jean Paul, De Deyn, Peter P, Concari, Letizia, Brice, Alexis, Dubois, Bruno, Tschanz, JoAnn, Fitzpatrick, Annette L, Kukull, Walter A, Bullido, María J, Coto, Eliecer, Reiman, Eric M, Gallo, Maura, Scarpini, Elio, Tsuang, Debby W, Bonuccelli, Ubaldo, Rubinsztein, David C, Bras, Jose, Guerreiro, Rita, Lovestone, Simon, Owen, Michael J, Cruchaga, Carlos, Powell, John, De Jager, Philip L, Rujescu, Dan, Ortega-Cubero, Sara, Ikram, M Arfan, Mayeux, Richard, Deleuze, Jean-François, Amin, Najaf, Amouyel, Philippe, van Duijn, Cornelia M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2017; Nature Publishing Group
• Subjects: 45/43; 631/208/205/2138; 692/699/375/365/1283; Adaptor Proteins, Signal Transducing - genetics; Agriculture; Alzheimer Disease - genetics; Alzheimer's disease; Amino Acid Sequence; Animal Genetics and Genomics; Bioinformatics; Biomedicine; Cancer Research; Case-Control Studies; Consortia; Development and progression; Disease control; DNA methylation; DNA microarrays; Exome - genetics; Gene Expression Profiling; Gene Frequency; Gene Function; Genes; Genetic aspects; Genetic Predisposition to Disease - genetics; Genetic variation; Genomes; Genomics; Genotype; Genotypes; Genotyping; Human Genetics; Humans; Immune response; Immune system; Immunity; Immunity (Disease); Immunity, Innate - genetics; Innate immunity; letter; Life Sciences; Linkage Disequilibrium; Membrane Glycoproteins - genetics; Microglia; Microglia - metabolism; Neurodegenerative diseases; Neurons and Cognition; Odds Ratio; Phospholipase C gamma - genetics; Physiological aspects; Polymorphism, Single Nucleotide; Protein interaction; Protein Interaction Maps - genetics; Proteins; Receptors, Immunologic - genetics; Sequence Homology, Amino Acid; Studies; United States; United Kingdom; Netherlands

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2 , ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes...