Two New Genes Linked to Alzheimer’s Risk

Summary: Researchers from Cardiff University have identified two new genes that can influence a person’s risk of developing Alzheimer’s disease.

Source: Cardiff University.

A team of researchers led by Cardiff University has identified two genes that influence a person’s risk of developing Alzheimer’s disease.

The new finding, which builds on the team’s previous work of identifying 24 susceptibility genes, enables a better understanding of the mechanisms underlying the disease and offers further hope in developing new treatments.

Dr Rebecca Sims from Cardiff University’s School of Medicine said: “In addition to identifying two genes that affect the risk of developing Alzheimer’s disease, our new research reveals a number of other genes and proteins that form a network likely to be important in its development. These particular genes, which suggest that immune cells in the brain play a causal role in the disease, are also very good targets for potential drug treatment.”

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, added: “The discovery of new genes is like finding puzzle pieces that biologists can start to fit together to build a complete picture of a disease.

“Alzheimer’s Research UK is proud to be supporting scientists at the cutting edge of this work as they continue to make valuable discoveries that are shaping our understanding of the disease. There are currently no treatments to slow the progression of Alzheimer’s and increased investment in research is vital so that we can capitalise on new findings and drive progress for people with the condition and their families.”

The two novel genes, which were not previously considered candidates for Alzheimer’s risk, were identified during a study which compared the DNA of tens of thousands of individuals with Alzheimer’s with aged-matched people who are free from the disease.

There are currently around 850,000 people in the UK with Alzheimer’s. During the course of the disease, proteins build up in the brain to form structures called plaques and tangles. The connections between nerve cells are lost, and eventually the nerve cells die and brain tissue volume is reduced. People with Alzheimer’s also have a shortage of some important chemicals in their brain. These chemical messengers help to transmit signals around the brain. When there is a shortage of them, the signals are not transmitted as effectively.

Dr Doug Brown, Director of Research and Development at Alzheimer’s Society, said: “Over 60% of people with dementia have Alzheimer’s disease, yet despite its prevalence we still don’t fully understand the complex causes of the disease.

Image shows a DNA strand.
The two novel genes, which were not previously considered candidates for Alzheimer’s risk, were identified during a study which compared the DNA of tens of thousands of individuals with Alzheimer’s with aged-matched people who are free from the disease.
NeuroscienceNews.com image is for illustrative purposes only.

“The discovery of two new risk genes for Alzheimer’s is an exciting advance that could help to deepen our understanding of what happens in the brains of people with the disease. These genes reinforce a critical role for special cells in the brain – called microglia – that are responsible for clearing up debris including damaged cells and proteins. Insights like this are vital to help unravel the complexities of Alzheimer’s disease and show researchers where to focus their efforts in the search for new, effective treatments.

“As a funder of this research, we’re delighted to see important progress being made. The UK Dementia Research Institute centre at Cardiff will now build on this discovery to investigate in detail the role of microglia in dementia and ultimately accelerate our progress towards finding a cure.”

About this neuroscience research article

Funding: Cardiff University’s involvement in the research was funded by the Alzheimer’s Society, The Medical Research Council (MRC), Welsh Government and Alzheimer’s Research UK.

Source: Julia Short – Cardiff University
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease” by Rebecca Sims, Sven J van der Lee, Adam C Naj, Céline Bellenguez, Nandini Badarinarayan, Johanna Jakobsdottir, Brian W Kunkle, Anne Boland, Rachel Raybould, Joshua C Bis, Eden R Martin, Benjamin Grenier-Boley, Stefanie Heilmann-Heimbach, Vincent Chouraki, Amanda B Kuzma, Kristel Sleegers, Maria Vronskaya, Agustin Ruiz, Robert R Graham, Robert Olaso, Per Hoffmann, Megan L Grove, Badri N Vardarajan, Mikko Hiltunen, Markus M Nöthen, Charles C White, Kara L Hamilton-Nelson, Jacques Epelbaum, Wolfgang Maier, Seung-Hoan Choi, Gary W Beecham, Cécile Dulary, Stefan Herms, Albert V Smith, Cory C Funk, Céline Derbois, Andreas J Forstner, Shahzad Ahmad, Hongdong Li, Delphine Bacq, Denise Harold, Claudia L Satizabal, Otto Valladares, Alessio Squassina, Rhodri Thomas, Jennifer A Brody, Liming Qu, Pascual Sánchez-Juan, Taniesha Morgan, Frank J Wolters, Yi Zhao, Florentino Sanchez Garcia, Nicola Denning, Myriam Fornage, John Malamon, Maria Candida Deniz Naranjo, Elisa Majounie, Thomas H Mosley, Beth Dombroski, David Wallon, Michelle K Lupton, Josée Dupuis, Patrice Whitehead, Laura Fratiglioni, Christopher Medway, Xueqiu Jian, Shubhabrata Mukherjee, Lina Keller, Kristelle Brown, Honghuang Lin, Laura B Cantwell, Francesco Panza, Bernadette McGuinness, Sonia Moreno-Grau, Jeremy D Burgess, Vincenzo Solfrizzi, Petra Proitsi, Hieab H Adams, Mariet Allen, Davide Seripa, Pau Pastor, L Adrienne Cupples, Nathan D Price, Didier Hannequin, Ana Frank-García, Daniel Levy, Paramita Chakrabarty, Paolo Caffarra, Ina Giegling, Alexa S Beiser, Vilmantas Giedraitis, Harald Hampel, Melissa E Garcia, Xue Wang, Lars Lannfelt, Patrizia Mecocci, Gudny Eiriksdottir, Paul K Crane, Florence Pasquier, Virginia Boccardi, Gianfranco Spalletta, Carolina Ceballos Diaz, Mark A Sager, Ron Munger, David C Rubinsztein, Annakaisa Haapasalo, Linda J Van Eldik, Debby W Tsuang, Christine Van Broeckhoven, Timothy W Behrens, William W Seeley, Gerard D Schellenberg, James T Becker, Manuel Mayhaus, Chuanhai Cao, Eliezer Masliah, Sarah Taylor, Murray Raskind, Anita L DeStefano, Wayne W Poon, Marla Gearing, Bernardino Ghetti, Bruno Vellas, David Mann, Christophe Tzourio, ARUK Consortium, Cornelia M van Duijn, Robert A Stern, Julie Williams, Duane Beekly, Constantine G Lyketsos, Eliecer Coto, Amy Braddel, Brian Lawlor, Alun Meggy, Michael J Owen, Mònica Díez Fairén, Reinhard Heun, Joan S Reisch, Joel H Kramer, Hakan Thonberg, Ekaterina Rogaeva, Isabel Henández, Carole Dufouil, Roberta Cecchetti, Maria Norton, Neill R Graff-Radford, Joshua W Miller, Thomas G Beach, Lenore J Launer, C Dirk Keene, Deborah C Mash, Chiara Cupidi, Hilkka Soininen, Joseph E Parisi, Matthew J Huentelman, Melanie Dunstan, Vivianna M Van Deerlin, Peter P De Deyn, Bruce L Miller, Charlene Thomas, Steven G Younkin, Howard J Rosen, Matt Hill, Russell H Swerdlow, Jean Paul Vonsattel, Carlos Cruchaga, Paola Bossù, Vincent Dermecourt, Gail P Jarvik, Marsel Mesulam, RoseMarie Brundin, John M Olichney, Maria Urbano, Kelley M Faber, Walter A Kukull, John H Growdon, Denis A Evans, Nilufer Ertekin-Taner, James B Leverenz, Charlotte Forsell, Benedetta Nacmias, Alberto Pilotto, M Ilyas Kamboh, Vernon S Pankratz, Nathalie Fievet, Imelda S Barber, Christiane Reitz, Peter A Holmans, Chiara Fenoglio, Kevin Morgan, Douglas R Galasko, Lesley Jones, Donald R Royall, Eric Boerwinkle, Daniela Galimberti, Julie A Schneider, Liana G Apostolova, Najaf Amin, Miquel Aguilar, David G Clark, Maria Serpente, Clive Holmes, Chris S Carlson, Susan M McCurry, Ronald C Petersen, Margaret A Pericak-Vance, John Keoni Kauwe, Angela Hodges, Andre G Uitterlinden, GERAD/PERADES, CHARGE, ADGC, EADI, Makrina Daniilidou, Elaine Peskind, Carlo Caltagirone, Eric M Reiman, John Collinge, Malcolm Dick, Sudha Seshadri, Ranjan Duara, Rita Guerreiro, Reinhold Schmidt, Perrie M Adams, Dominique Campion, Rafael Blesa, Maura Gallo, James R Burke, Frank Martiniuk, W T Longstreth Jr, Rebecca Sussams, Marina Arcaro, Alfredo Ramirez, Johannes Kornhuber, John C Morris, Andrew N McDavid, Barry Reisberg, John Morris, Regina M Carney, Christine M Hulette, Sebastien Engelborghs, Kathryn L Lunetta, Ammar Al-Chalabi, Peter St George-Hyslop, Alberto Lleó, Markus Leber, Rudolph E Tanzi, Susanne Moebus, Richard B Lipton, Feroze Golamaully, Anne Braae, Minerva M Carrasquillo, David A Bennett, Yuning Chen, Stephen Todd, Joseph T Hughes, Sara Ortega-Cubero, Bruce M Psaty, Charles DeCarli, Maria Donata Orfei, Eileen H Bigio, Henry L Paulson, Lei Yu, John Q Trojanowski, Michael Gill, Victoria Alvarez, David H Cribbs, Letizia Concari, Elizabeth A Crocco, Jean-François Dartigues, Wei Gu, Philip L De Jager, Craig S Atwood, Adam Boxer, James Turton, Paolo Bosco, Valur Emilsson, María J Bullido, Clinton B Wright, Annette L Fitzpatrick, Ge Li, Rachelle S Doody, Lon S Schneider, Ubaldo Bonuccelli, Erin Abner, Ronald L Hamilton, Joseph F Quinn, Simon Lovestone, Martin Dichgans, Jayanadra J Himali, Rachel Marshall, Matthew P Frosch, John Powell, John Hardy, Matthias Riemenschneider, Martin Scherer, Jordi Clarimón, Olivier Hanon, Salvatore Spina, Thomas J Fairchild, Jerome I Rotter, Steven E Arnold, Anne Kinhult-Stählbom, Jennifer Williamson, Sandra Weintraub, Amalia Cecilia Bruni, Thomas J Montine, Ann C McKee, Allan I Levey, Thor Aspelund, Chuang-Kuo Wu, Wayne C McCormick, Marilyn S Albert, Dan Rujescu, Tatiana M Foroud, Keeley Brookes, Eleonora Sacchinelli, Frank M LaFerla, Fabienne Garzia, Qiong Yang, Martin Ingelsson, Kenneth B Fallon, Helena C Chui, William Perry, Yoland Aladro Benito, Andrew P Lieberman, Lluis Tarraga, Joshua A Sonnen, Vilmundur Gudnason, Christopher J O’Donnell, Kathleen A Welsh-Bohmer, Rik Vandenberghe, Janet Johnston, Thomas D Bird, Mary Sano, Onofre Combarros, Carol Brayne, Harry V Vinters, Roger N Rosenberg, Erik D Roberson, Valentina Escott-Price, Roger L Albin, Juan C Troncoso, Jeffrey M Burns, Aimee Pierce, Jill R Murrell, Elio Scarpini, Eric B Larson, Nigel J Cairns, Ashley R Winslow, Daniel H Geschwind, Peter Passmore, Steffi Riedel-Heller, Thomas S Wingo, Martin R Farlow, Jonathan L Haines, Karen Ritchie, Christopher E Shaw, Raffaele Giovanni Maletta, Helena Schmidt, Huntington Potter, Gyungah Jun, Carmen Muñoz Fernadez, Bruno Dubois, Bradley T Hyman, Jeffrey A Kaye, Anna Karydas, Frank Jessen, Ashok Raj, Alexis Brice, Magda Tsolaki, Chang-En Yu, Lindsay A Farrer, John R Gilbert, Jose Bras, Merce Boada, Nick C Fox, Amanda J Myers, Deborah Blacker, Joseph D Buxbaum, Oscar L Lopez, Neil W Kowall, Caroline Graff, James J Lah, Tricia A Thornton-Wells, Juan Fortea, Carlo Masullo, Sabrina Pichler, Lawrence S Honig, Dennis W Dickson, John M Ringman, Sandro Sorbi, Ryan M Huebinger, Clinton T Baldwin, Andrew J Saykin, Oscar Sotolongo-Grau, Claudine Berr, Seppo Helisalmi, James D Bowen, Lee-Way Jin, Kirk C Wilhelmsen, Ronald Kim, Yogen Patel, Gislain Septier, Jean-Charles Lambert, Jean-François Deleuze, Sandra Barral, Steven L Carroll, Annette M Hartmann, Oliver Peters, Albert Hofman, Anne Maria Koivisto, Hakon Hakonarson, Iwona Kloszewska, Robert C Barber, David Carrell, Amanda G Smith, Alison M Goate, Sid O’Bryant, Jade Chapman, David W Fardo, David Craig, Li-San Wang, Simon Mead, Jenny Lord, JoAnn Tschanz, Robert C Green, Mindy J Katz, Antonio Daniele, Chris Corcoran, Lisa L Barnes, Sanjay Asthana, Lena Lilius, Shuo Li, Antonio Ciaramella, Carol A Miller, Fernando Rivadeneira, Lena Kilander, Randall L Woltjer, Philippe Amouyel, Bradley F Boeve, Cynthia M Carlsson, Steven Ferris, Daniel C Marson, Amy Gerrish, Todd E Golde, Lindy E Harrell, Aoibhinn Lynch, Richard Mayeux, Michael C O’Donovan, M Arfan Ikram, Michelangelo Mancuso & James Uphill in Nature Genetics. Published online June 20 2017 doi:10.1038/ng.3916

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]Cardiff University “Two New Genes Linked to Alzheimer’s Risk.” NeuroscienceNews. NeuroscienceNews, 17 July 2017.
<https://neurosciencenews.com/two-genes-alzheimers-7094/>.[/cbtab][cbtab title=”APA”]Cardiff University (2017, July 17). Two New Genes Linked to Alzheimer’s Risk. NeuroscienceNew. Retrieved July 17, 2017 from https://neurosciencenews.com/two-genes-alzheimers-7094/[/cbtab][cbtab title=”Chicago”]Cardiff University “Two New Genes Linked to Alzheimer’s Risk.” https://neurosciencenews.com/two-genes-alzheimers-7094/ (accessed July 17, 2017).[/cbtab][/cbtabs]


Abstract

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

We identified rare coding variants associated with Alzheimer’s disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

“Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease” by Rebecca Sims, Sven J van der Lee, Adam C Naj, Céline Bellenguez, Nandini Badarinarayan, Johanna Jakobsdottir, Brian W Kunkle, Anne Boland, Rachel Raybould, Joshua C Bis, Eden R Martin, Benjamin Grenier-Boley, Stefanie Heilmann-Heimbach, Vincent Chouraki, Amanda B Kuzma, Kristel Sleegers, Maria Vronskaya, Agustin Ruiz, Robert R Graham, Robert Olaso, Per Hoffmann, Megan L Grove, Badri N Vardarajan, Mikko Hiltunen, Markus M Nöthen, Charles C White, Kara L Hamilton-Nelson, Jacques Epelbaum, Wolfgang Maier, Seung-Hoan Choi, Gary W Beecham, Cécile Dulary, Stefan Herms, Albert V Smith, Cory C Funk, Céline Derbois, Andreas J Forstner, Shahzad Ahmad, Hongdong Li, Delphine Bacq, Denise Harold, Claudia L Satizabal, Otto Valladares, Alessio Squassina, Rhodri Thomas, Jennifer A Brody, Liming Qu, Pascual Sánchez-Juan, Taniesha Morgan, Frank J Wolters, Yi Zhao, Florentino Sanchez Garcia, Nicola Denning, Myriam Fornage, John Malamon, Maria Candida Deniz Naranjo, Elisa Majounie, Thomas H Mosley, Beth Dombroski, David Wallon, Michelle K Lupton, Josée Dupuis, Patrice Whitehead, Laura Fratiglioni, Christopher Medway, Xueqiu Jian, Shubhabrata Mukherjee, Lina Keller, Kristelle Brown, Honghuang Lin, Laura B Cantwell, Francesco Panza, Bernadette McGuinness, Sonia Moreno-Grau, Jeremy D Burgess, Vincenzo Solfrizzi, Petra Proitsi, Hieab H Adams, Mariet Allen, Davide Seripa, Pau Pastor, L Adrienne Cupples, Nathan D Price, Didier Hannequin, Ana Frank-García, Daniel Levy, Paramita Chakrabarty, Paolo Caffarra, Ina Giegling, Alexa S Beiser, Vilmantas Giedraitis, Harald Hampel, Melissa E Garcia, Xue Wang, Lars Lannfelt, Patrizia Mecocci, Gudny Eiriksdottir, Paul K Crane, Florence Pasquier, Virginia Boccardi, Gianfranco Spalletta, Carolina Ceballos Diaz, Mark A Sager, Ron Munger, David C Rubinsztein, Annakaisa Haapasalo, Linda J Van Eldik, Debby W Tsuang, Christine Van Broeckhoven, Timothy W Behrens, William W Seeley, Gerard D Schellenberg, James T Becker, Manuel Mayhaus, Chuanhai Cao, Eliezer Masliah, Sarah Taylor, Murray Raskind, Anita L DeStefano, Wayne W Poon, Marla Gearing, Bernardino Ghetti, Bruno Vellas, David Mann, Christophe Tzourio, ARUK Consortium, Cornelia M van Duijn, Robert A Stern, Julie Williams, Duane Beekly, Constantine G Lyketsos, Eliecer Coto, Amy Braddel, Brian Lawlor, Alun Meggy, Michael J Owen, Mònica Díez Fairén, Reinhard Heun, Joan S Reisch, Joel H Kramer, Hakan Thonberg, Ekaterina Rogaeva, Isabel Henández, Carole Dufouil, Roberta Cecchetti, Maria Norton, Neill R Graff-Radford, Joshua W Miller, Thomas G Beach, Lenore J Launer, C Dirk Keene, Deborah C Mash, Chiara Cupidi, Hilkka Soininen, Joseph E Parisi, Matthew J Huentelman, Melanie Dunstan, Vivianna M Van Deerlin, Peter P De Deyn, Bruce L Miller, Charlene Thomas, Steven G Younkin, Howard J Rosen, Matt Hill, Russell H Swerdlow, Jean Paul Vonsattel, Carlos Cruchaga, Paola Bossù, Vincent Dermecourt, Gail P Jarvik, Marsel Mesulam, RoseMarie Brundin, John M Olichney, Maria Urbano, Kelley M Faber, Walter A Kukull, John H Growdon, Denis A Evans, Nilufer Ertekin-Taner, James B Leverenz, Charlotte Forsell, Benedetta Nacmias, Alberto Pilotto, M Ilyas Kamboh, Vernon S Pankratz, Nathalie Fievet, Imelda S Barber, Christiane Reitz, Peter A Holmans, Chiara Fenoglio, Kevin Morgan, Douglas R Galasko, Lesley Jones, Donald R Royall, Eric Boerwinkle, Daniela Galimberti, Julie A Schneider, Liana G Apostolova, Najaf Amin, Miquel Aguilar, David G Clark, Maria Serpente, Clive Holmes, Chris S Carlson, Susan M McCurry, Ronald C Petersen, Margaret A Pericak-Vance, John Keoni Kauwe, Angela Hodges, Andre G Uitterlinden, GERAD/PERADES, CHARGE, ADGC, EADI, Makrina Daniilidou, Elaine Peskind, Carlo Caltagirone, Eric M Reiman, John Collinge, Malcolm Dick, Sudha Seshadri, Ranjan Duara, Rita Guerreiro, Reinhold Schmidt, Perrie M Adams, Dominique Campion, Rafael Blesa, Maura Gallo, James R Burke, Frank Martiniuk, W T Longstreth Jr, Rebecca Sussams, Marina Arcaro, Alfredo Ramirez, Johannes Kornhuber, John C Morris, Andrew N McDavid, Barry Reisberg, John Morris, Regina M Carney, Christine M Hulette, Sebastien Engelborghs, Kathryn L Lunetta, Ammar Al-Chalabi, Peter St George-Hyslop, Alberto Lleó, Markus Leber, Rudolph E Tanzi, Susanne Moebus, Richard B Lipton, Feroze Golamaully, Anne Braae, Minerva M Carrasquillo, David A Bennett, Yuning Chen, Stephen Todd, Joseph T Hughes, Sara Ortega-Cubero, Bruce M Psaty, Charles DeCarli, Maria Donata Orfei, Eileen H Bigio, Henry L Paulson, Lei Yu, John Q Trojanowski, Michael Gill, Victoria Alvarez, David H Cribbs, Letizia Concari, Elizabeth A Crocco, Jean-François Dartigues, Wei Gu, Philip L De Jager, Craig S Atwood, Adam Boxer, James Turton, Paolo Bosco, Valur Emilsson, María J Bullido, Clinton B Wright, Annette L Fitzpatrick, Ge Li, Rachelle S Doody, Lon S Schneider, Ubaldo Bonuccelli, Erin Abner, Ronald L Hamilton, Joseph F Quinn, Simon Lovestone, Martin Dichgans, Jayanadra J Himali, Rachel Marshall, Matthew P Frosch, John Powell, John Hardy, Matthias Riemenschneider, Martin Scherer, Jordi Clarimón, Olivier Hanon, Salvatore Spina, Thomas J Fairchild, Jerome I Rotter, Steven E Arnold, Anne Kinhult-Stählbom, Jennifer Williamson, Sandra Weintraub, Amalia Cecilia Bruni, Thomas J Montine, Ann C McKee, Allan I Levey, Thor Aspelund, Chuang-Kuo Wu, Wayne C McCormick, Marilyn S Albert, Dan Rujescu, Tatiana M Foroud, Keeley Brookes, Eleonora Sacchinelli, Frank M LaFerla, Fabienne Garzia, Qiong Yang, Martin Ingelsson, Kenneth B Fallon, Helena C Chui, William Perry, Yoland Aladro Benito, Andrew P Lieberman, Lluis Tarraga, Joshua A Sonnen, Vilmundur Gudnason, Christopher J O’Donnell, Kathleen A Welsh-Bohmer, Rik Vandenberghe, Janet Johnston, Thomas D Bird, Mary Sano, Onofre Combarros, Carol Brayne, Harry V Vinters, Roger N Rosenberg, Erik D Roberson, Valentina Escott-Price, Roger L Albin, Juan C Troncoso, Jeffrey M Burns, Aimee Pierce, Jill R Murrell, Elio Scarpini, Eric B Larson, Nigel J Cairns, Ashley R Winslow, Daniel H Geschwind, Peter Passmore, Steffi Riedel-Heller, Thomas S Wingo, Martin R Farlow, Jonathan L Haines, Karen Ritchie, Christopher E Shaw, Raffaele Giovanni Maletta, Helena Schmidt, Huntington Potter, Gyungah Jun, Carmen Muñoz Fernadez, Bruno Dubois, Bradley T Hyman, Jeffrey A Kaye, Anna Karydas, Frank Jessen, Ashok Raj, Alexis Brice, Magda Tsolaki, Chang-En Yu, Lindsay A Farrer, John R Gilbert, Jose Bras, Merce Boada, Nick C Fox, Amanda J Myers, Deborah Blacker, Joseph D Buxbaum, Oscar L Lopez, Neil W Kowall, Caroline Graff, James J Lah, Tricia A Thornton-Wells, Juan Fortea, Carlo Masullo, Sabrina Pichler, Lawrence S Honig, Dennis W Dickson, John M Ringman, Sandro Sorbi, Ryan M Huebinger, Clinton T Baldwin, Andrew J Saykin, Oscar Sotolongo-Grau, Claudine Berr, Seppo Helisalmi, James D Bowen, Lee-Way Jin, Kirk C Wilhelmsen, Ronald Kim, Yogen Patel, Gislain Septier, Jean-Charles Lambert, Jean-François Deleuze, Sandra Barral, Steven L Carroll, Annette M Hartmann, Oliver Peters, Albert Hofman, Anne Maria Koivisto, Hakon Hakonarson, Iwona Kloszewska, Robert C Barber, David Carrell, Amanda G Smith, Alison M Goate, Sid O’Bryant, Jade Chapman, David W Fardo, David Craig, Li-San Wang, Simon Mead, Jenny Lord, JoAnn Tschanz, Robert C Green, Mindy J Katz, Antonio Daniele, Chris Corcoran, Lisa L Barnes, Sanjay Asthana, Lena Lilius, Shuo Li, Antonio Ciaramella, Carol A Miller, Fernando Rivadeneira, Lena Kilander, Randall L Woltjer, Philippe Amouyel, Bradley F Boeve, Cynthia M Carlsson, Steven Ferris, Daniel C Marson, Amy Gerrish, Todd E Golde, Lindy E Harrell, Aoibhinn Lynch, Richard Mayeux, Michael C O’Donovan, M Arfan Ikram, Michelangelo Mancuso & James Uphill in Nature Genetics. Published online June 20 2017 doi:10.1038/ng.3916

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