Article
Environmental Sciences
Xurui Jin, Chang Shu, Yi Zeng, Liming Liang, John S. Ji
Summary: The study explored the impact of greenness in the residential environment on the cognitive function of individuals with genetic predisposition to Alzheimer's disease, finding that for those with low genetic risk, higher greenness was associated with reduced risk of cognitive impairment.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Biochemistry & Molecular Biology
Jonathan L. Hess, Daniel S. Tylee, Manuel Mattheisen, Anders D. Borglum, Thomas D. Als, Jakob Grove, Thomas Werge, Preben Bo Mortensen, Ole Mors, Merete Nordentoft, David M. Hougaard, Jonas Byberg-Grauholm, Marie Baekvad-Hansen, Tiffany A. Greenwood, Ming T. Tsuang, David Curtis, Stacy Steinberg, Engilbert Sigurdsson, Hreinn Stefansson, Kari Stefansson, Howard J. Edenberg, Peter Holmans, Stephen Faraone, Stephen J. Glatt
Summary: This study proposed a theoretical framework based on genetic variations that promote resilience to highly heritable polygenic disorders, such as schizophrenia. By establishing a procedure to identify unaffected individuals with relatively high polygenic risk for the disease and generating the first known polygenic resilience score, this work laid a foundation for finding resilience variants for any complex, heritable disorder.
MOLECULAR PSYCHIATRY
(2021)
Article
Clinical Neurology
Xiao-Yu He, Bang-Sheng Wu, Kevin Kuo, Wei Zhang, Qing Ma, Shi-Tong Xiang, Yu-Zhu Li, Zi-yi Wang, Qiang Dong, Jian-Feng Feng, Wei Cheng, Jin-Tai Yu
Summary: This study used large-scale genome-wide association datasets to explore the correlations between genetic risk for Alzheimer's disease (AD) and regional brain structures at different ages. The results suggest that genetic loading for AD influences brain structures in a highly dynamic manner, with different patterns observed at different ages.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Review
Behavioral Sciences
E. Eeltink, M. Z. Van der Horst, J. R. Zinkstok, C. M. Aalfs, J. J. Luykx
Summary: Polygenic risk scores (PRS) have the potential to identify individuals at-risk for psychiatric disorders, optimize treatment, and improve prognostic accuracy. However, integrating PRS into genetic counseling sessions remains challenging due to uncertainties in risk prediction and other concerns. Lessons learned from other medical fields could benefit the incorporation of PRS in psychiatric genetic counseling, including integrating PRS with environmental factors, conducting large-scale studies, and using reproducible methods for cross-validation.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Clinical Neurology
Hengameh Shams, Xiaorong Shao, Adam Santaniello, Gina Kirkish, Adil Harroud, Qin Ma, Noriko Isobe, Catherine Schaefer, Jacob L. McCauley, Bruce A. C. Cree, Alessandro Didonna, Sergio E. Baranzini, Nikolaos A. Patsopoulos, Stephen L. Hauser, Lisa F. Barcellos, Roland G. Henry, Jorge R. Oksenberg
Summary: Polygenic inheritance plays a pivotal role in multiple sclerosis susceptibility. The development of polygenic risk scores (PRS) can assess disease status and severity, providing enhanced risk assessment and radiographic outcomes. This study indicates important associations of PRS with risk assessment and tissue injury outcomes, potentially informing targeted screening and prevention strategies.
Article
Clinical Neurology
Emma S. Luckett, Yasmina Abakkouy, Mariska Reinartz, Katarzyna Adamczuk, Jolien Schaeverbeke, Sare Verstockt, Steffi De Meyer, Koen Van Laere, Patrick Dupont, Isabelle Cleynen, Rik Vandenberghe
Summary: This study found that specific AD polygenic risk scores are associated with amyloid accumulation in the asymptomatic phase of Alzheimer's disease.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Environmental Sciences
Cheng Xu, Zhenkun Weng, Qian Liu, Jin Xu, Jingjia Liang, Wenxiang Li, Jia Hu, Tao Huang, Yong Zhou, Aihua Gu
Summary: This study aimed to investigate the effects of air pollutants on the risk of osteoporosis and the modifying effect of genetic predisposition. The results showed that exposure to air pollutants, particularly PM2.5, NO2, and NOx, was associated with an increased risk of osteoporosis. The risk was even higher in populations with high genetic risk. Air pollutants and genetic variants exerted additive effects on the risk of osteoporosis.
ENVIRONMENT INTERNATIONAL
(2022)
Article
Clinical Neurology
Hui Liu, Mohammad Dehestani, Cornelis Blauwendraat, Mary B. Makarious, Hampton Leonard, Jonggeol J. Kim, Claudia Schulte, Alastair Noyce, Benjamin M. Jacobs, Isabelle Foote, Manu Sharma, Mike Nalls, Andrew Singleton, Thomas Gasser, Sara Bandres-Ciga
Summary: This study aims to understand why some individuals with high genetic risk do not develop Parkinson's disease (PD). Using large datasets of genetic data, the study found that a higher genetic resilience score was associated with a lower risk for PD. The study also identified potential genes and pathways related to resilience against PD.
ANNALS OF NEUROLOGY
(2022)
Article
Clinical Neurology
Anna Zettergren, Jodie Lord, Nicholas J. Ashton, Andrea L. Benedet, Thomas K. Karikari, Juan Lantero Rodriguez, Anniina Snellman, Marc Suarez-Calvet, Petroula Proitsi, Henrik Zetterberg, Kaj Blennow
Summary: The study revealed that polygenic risk for AD, including APOE, was associated with plasma p-tau181 regardless of diagnostic or A beta pathology status, while polygenic risk for AD beyond APOE was only linked to plasma p-tau181 in individuals with MCI and A beta positivity.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Rheumatology
Chien-Yu Lin, Ya-Sian Chang, Ting-Yuan Liu, Chung-Ming Huang, Chin-Chun Chung, Yu-Chia Chen, Fuu-Jen Tsai, Jan-Gowth Chang, Shun-Jen Chang
Summary: This study identified genetic variants and polygenic risk scores related to female gout and asymptomatic hyperuricaemia (AH) through a genome-wide association study (GWAS). The variants in the SLC2A9 gene were found to be the major genetic factors associated with gout in females aged >= 50, while variants in the SLC2A9, ZNF518B, PKD2, and ABCG2 genes were significantly related to AH in both age groups. The polygenic risk score provided a more accurate prediction of gout and AH.
Article
Cardiac & Cardiovascular Systems
Carolina Roselli, Mengyao Yu, Victor Nauffal, Adrien Georges, Qiong Yang, Katie Love, Lu-Chen Weng, Francesca N. Delling, Svetlana R. Maurya, Maren Schrolkamp, Jacob Tfelt-Hansen, Albert Hagege, Xavier Jeunemaitre, Stephanie Debette, Philippe Amouyel, Wyliena Guan, Jochen D. Muehlschlegel, Simon C. Body, Svati Shah, Zainab Samad, Sergiy Kyryachenko, Carol Haynes, Michiel Rienstra, Thierry Le Tourneau, Vincent Probst, Ronan Roussel, Inez J. Wijdh-Den Hamer, Joylene E. Siland, Kirk U. Knowlton, Jean Jacques Schott, Robert A. Levine, Emelia J. Benjamin, Ramachandran S. Vasan, Benjamin D. Horne, Joseph B. Muhlestein, Giovanni Benfari, Maurice Enriquez-Sarano, Andrea Natale, Sanghamitra Mohanty, Chintan Trivedi, Moore B. Shoemaker, Zachary T. Yoneda, Quinn S. Wells, Michael T. Baker, Eric Farber-Eger, Hector Michelena, Alicia Lundby, Russell A. Norris, Susan A. Slaugenhaupt, Christian Dina, Steven A. Lubitz, Nabila Bouatia-Naji, Patrick T. Ellinor, David J. Milan
Summary: We conducted a meta-analysis of six genome-wide association studies and identified 14 loci associated with mitral valve prolapse (MVP). Integration of epigenetic, transcriptional, and proteomic data revealed potential candidate genes for MVP. Additionally, we developed a polygenic risk score (PRS) for MVP that improved risk prediction beyond traditional clinical factors.
EUROPEAN HEART JOURNAL
(2022)
Article
Biology
Tianyuan Lu, Vincenzo Forgetta, J. Brent Richards, Celia M. T. Greenwood
Summary: This study developed a latent factor model to quantify trait heritability beyond what is captured by a common variant-based polygenic risk score, and incorporated family history into genetic risk prediction models, leading to improved risk prediction accuracy.
COMMUNICATIONS BIOLOGY
(2022)
Article
Geriatrics & Gerontology
Ted Lawingco, Sultan Chaudhury, Keeley J. Brookes, Tamar Guetta-Baranes, Rita Guerreiro, Jose Bras, John Hardy, Paul Francis, Alan Thomas, Olivia Belbin, Kevin Morgan
Summary: Synapse loss is an early event in late-onset Alzheimer's disease, and a polygenic risk score (PRS) restricted to synapse-encoding loci was found to be predictive of LOAD with high accuracy. This study also revealed that genes encoding synapses are enriched for LOAD risk-modifying loci.
NEUROBIOLOGY OF AGING
(2021)
Article
Geriatrics & Gerontology
Mingzhou Fu, Timothy S. Chang
Summary: In this study, a phenome-wide association study (PheWAS) was conducted to investigate the genetic risk of Alzheimer's disease (AD) and its association with other disease conditions. The results showed a strong association between AD genetic risk and AD phenotype in European ancestry. Furthermore, a significant association between AD genetic risk and gouty arthropathy was observed, but it was not a causal relationship.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Neurosciences
Hongliang Liu, Michael Lutz, Sheng Luo
Summary: This study aimed to evaluate the associations between polygenic risk scores (PRS) and progression to Alzheimer's disease (AD) from mild cognitive impairment (MCI), changes in cognitive impairment, and biomarkers. The results showed that PRS constructed with SNPs reaching genome-wide significance predicted the progression from MCI to AD, and was associated with changes in cognitive impairment, levels of biomarkers, and brain volumes. The findings suggest that PRS can be useful for predicting time to AD and other clinical changes after MCI diagnosis.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neurosciences
Grazia Daniela Femminella, Denise Harold, James Scott, Julie Williams, Paul Edison
Summary: This study investigated associations between pathway-specific polygenic risk scores and AD biomarkers in patients with MCI and healthy controls. It found that different pathway risk scores were associated with cognitive measures, amyloid deposition, and brain metabolism changes, highlighting the influence of specific genes on different pathways in AD.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Review
Neurosciences
Rachel Raybould, Rebecca Sims
Summary: Sporadic Alzheimer's disease is a complex genetic disease, and approximately half of its heritability remains unexplained. The Dark Genome, regions not assayed by mainstream technology, may hold large structural DNA variants relevant to disease risk. Identifying such novel protein-coding structural variations could lead to new drug targets for AD.
Article
Genetics & Heredity
Sarah M. Carpanini, Janet C. Harwood, Emily Baker, Megan Torvell, Rebecca Sims, Julie Williams, B. Paul Morgan
Summary: Late-onset Alzheimer's disease is a neurodegenerative disease with uncertain etiology. Research suggests that complement genes may be associated with the risk of the disease, particularly CLU and CR1 genes, but further studies are needed for confirmation.
Article
Biochemistry & Molecular Biology
Emily Maguire, Georgina E. Menzies, Thomas Phillips, Michael Sasner, Harriet M. Williams, Magdalena A. Czubala, Neil Evans, Emma L. Cope, Rebecca Simss, Gareth R. Howell, Emyr Lloyd-Evans, Julie Williams, Nicholas D. Allen, Philip R. Taylor
Summary: Studies have revealed that the PLC gamma 2-R522 variant may offer protection against Alzheimer's disease (AD) by influencing cellular function, suggesting its potential as a therapeutic target for future treatments.
Article
Neurosciences
Ioanna Katzourou, Ganna Leonenko, Dobril Ivanov, Alun Meggy, Rachel Marshall, Rebecca Sims, Julie Williams, Peter Holmans, Valentina Escott-Price
Summary: This study aimed to explore the genetic architecture of cognitive decline in AD patients, and found no significant association between APOE ε2 or ε4 alleles and the rate of cognitive decline. Further exploration is needed to uncover possible genetic variants that affect the rate of decline in patients with AD.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Mary Ann A. DeMichele-Sweet, Lambertus Klei, Byron Creese, Janet C. Harwood, Elise A. Weamer, Lora McClain, Rebecca Sims, Isabel Hernandez, Sonia Moreno-Grau, Lluis Tarraga, Merce Boada, Emilio Alarcon-Martin, Sergi Valero, Yushi Liu, Basavaraj Hooli, Dag Aarsland, Geir Selbaek, Sverre Bergh, Arvid Rongve, Ingvild Saltvedt, Havard K. Skjellegrind, Bo Engdahl, Eystein Stordal, Ole A. Andreassen, Srdjan Djurovic, Lavinia Athanasiu, Davide Seripa, Barbara Borroni, Diego Albani, Gianluigi Forloni, Patrizia Mecocci, Alessandro Serretti, Diana De Ronchi, Antonis Politis, Julie Williams, Richard Mayeux, Tatiana Foroud, Agustin Ruiz, Clive Ballard, Peter Holmans, Oscar L. Lopez, M. Ilyas Kamboh, Bernie Devlin, Robert A. Sweet
Summary: Psychotic symptoms in Alzheimer's disease are common and have genetic components, with significant associations found in two loci - ENPP6 and SUMF1. AD + P shows negative genetic correlations with cognitive and educational attainment, and positive genetic correlations with depressive symptoms. This study provides insights into the genetic architecture of psychosis in Alzheimer's disease.
MOLECULAR PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Ganna Leonenko, Emily Baker, Joshua Stevenson-Hoare, Annerieke Sierksma, Mark Fiers, Julie Williams, Bart de Strooper, Valentina Escott-Price
Summary: Polygenic Risk Scores for Alzheimer's disease offer unique possibilities for reliably identifying individuals at high and low risk. The study shows that the best prediction accuracy is achieved with a model including APOE and a polygenic score excluding APOE. Standardizing PRS against the population mean makes individuals' scores comparable between studies.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Itziar de Rojas, Sonia Moreno-Grau, Niccolo Tesi, Benjamin Grenier-Boley, Victor Andrade, Iris E. Jansen, Nancy L. Pedersen, Najada Stringa, Anna Zettergren, Isabel Hernandez, Laura Montrreal, Carmen Antunez, Anna Antonell, Rick M. Tankard, Joshua C. Bis, Rebecca Sims, Celine Bellenguez, Ines Quintela, Antonio Gonzalez-Perez, Miguel Calero, Emilio Franco-Macias, Juan Macias, Rafael Blesa, Laura Cervera-Carles, Manuel Menendez-Gonzalez, Ana Frank-Garcia, Jose Luis Royo, Fermin Moreno, Raquel Huerto Vilas, Miquel Baquero, Monica Diez-Fairen, Carmen Lage, Sebastian Garcia-Madrona, Pablo Garcia-Gonzalez, Emilio Alarcon-Martin, Sergi Valero, Oscar Sotolongo-Grau, Abbe Ullgren, Adam C. Naj, Afina W. Lemstra, Alba Benaque, Alba Perez-Cordon, Alberto Benussi, Alberto Rabano, Alessandro Padovani, Alessio Squassina, Alexandre de Mendonca, Alfonso Arias Pastor, Almar A. L. Kok, Alun Meggy, Ana Belen Pastor, Ana Espinosa, Anais Corma-Gomez, Angel Martin Montes, Angela Sanabria, Anita L. DeStefano, Anja Schneider, Annakaisa Haapasalo, Anne Kinhult Stahlbom, Anne Tybjaerg-Hansen, Annette M. Hartmann, Annika Spottke, Arturo Corbaton-Anchuelo, Arvid Rongve, Barbara Borroni, Beatrice Arosio, Benedetta Nacmias, Borge G. Nordestgaard, Brian W. Kunkle, Camille Charbonnier, Carla Abdelnour, Carlo Masullo, Carmen Martinez Rodriguez, Carmen Munoz-Fernandez, Carole Dufouil, Caroline Graff, Catarina B. Ferreira, Caterina Chillotti, Chandra A. Reynolds, Chiara Fenoglio, Christine Van Broeckhoven, Christopher Clark, Claudia Pisanu, Claudia L. Satizabal, Clive Holmes, Dolores Buiza-Rueda, Dag Aarsland, Dan Rujescu, Daniel Alcolea, Daniela Galimberti, David Wallon, Davide Seripa, Edna Gruenblatt, Efthimios Dardiotis, Emrah Duezel, Elio Scarpini, Elisa Conti, Elisa Rubino, Ellen Gelpi, Eloy Rodriguez-Rodriguez, Emmanuelle Duron, Eric Boerwinkle, Evelyn Ferri, Fabrizio Tagliavini, Fahri Kucukali, Florence Pasquier, Florentino Sanchez-Garcia, Francesca Mangialasche, Frank Jessen, Gael Nicolas, Geir Selbaek, Gemma Ortega, Genevieve Chene, Georgios Hadjigeorgiou, Giacomina Rossi, Gianfranco Spalletta, Giorgio Giaccone, Giulia Grande, Giuliano Binetti, Goran Papenberg, Harald Hampel, Henri Bailly, Henrik Zetterberg, Hilkka Soininen, Ida K. Karlsson, Ignacio Alvarez, Ildebrando Appollonio, Ina Giegling, Ingmar Skoog, Ingvild Saltvedt, Innocenzo Rainero, Irene Rosas Allende, Jakub Hort, Janine Diehl-Schmid, Jasper Van Dongen, Jean-Sebastien Vidal, Jenni Lehtisalo, Jens Wiltfang, Jesper Qvist Thomassen, Johannes Kornhuber, Jonathan L. Haines, Jonathan Vogelgsang, Juan A. Pineda, Juan Fortea, Julius Popp, Juergen Deckert, Katharina Buerger, Kevin Morgan, Klaus Fliessbach, Kristel Sleegers, Laura Molina-Porcel, Lena Kilander, Leonie Weinhold, Lindsay A. Farrer, Li-San Wang, Luca Kleineidam, Lucia Farotti, Lucilla Parnetti, Lucio Tremolizzo, Lucrezia Hausner, Luisa Benussi, Lutz Froelich, M. Arfan Ikram, M. Candida Deniz-Naranjo, Magda Tsolaki, Maitee Rosende-Roca, Malin Lowenmark, Marc Hulsman, Marco Spallazzi, Margaret A. Pericak-Vance, Margaret Esiri, Maria Bernal Sanchez-Arjona, Maria Carolina Dalmasso, Maria Teresa Martinez-Larrad, Marina Arcaro, Markus M. Noethen, Marta Fernandez-Fuertes, Martin Dichgans, Martin Ingelsson, Martin J. Herrmann, Martin Scherer, Martin Vyhnalek, Mary H. Kosmidis, Mary Yannakoulia, Matthias Schmid, Michael Ewers, Michael T. Heneka, Michael Wagner, Michela Scamosci, Miia Kivipelto, Mikko Hiltunen, Miren Zulaica, Montserrat Alegret, Myriam Fornage, Natalia Roberto, Natasja M. van Schoor, Nazib M. Seidu, Nerisa Banaj, Nicola J. Armstrong, Nikolaos Scarmeas, Norbert Scherbaum, Oliver Goldhardt, Oliver Hanon, Oliver Peters, Olivia Anna Skrobot, Olivier Quenez, Ondrej Lerch, Paola Bossu, Paolo Caffarra, Paolo Dionigi Rossi, Paraskevi Sakka, Per Hoffmann, Peter A. Holmans, Peter Fischer, Peter Riederer, Qiong Yang, Rachel Marshall, Rajesh N. Kalaria, Richard Mayeux, Rik Vandenberghe, Roberta Cecchetti, Roberta Ghidoni, Ruth Frikke-Schmidt, Sandro Sorbi, Sara Hagg, Sebastiaan Engelborghs, Seppo Helisalmi, Sigrid Botne Sando, Silke Kern, Silvana Archetti, Silvia Boschi, Silvia Fostinelli, Silvia Gil, Silvia Mendoza, Simon Mead, Simona Ciccone, Srdjan Djurovic, Stefanie Heilmann-Heimbach, Steffi Riedel-Heller, Teemu Kuulasmaa, Teodoro del Ser, Thibaud Lebouvier, Thomas Polak, Tiia Ngandu, Timo Grimmer, Valentina Bessi, Valentina Escott-Price, Vilmantas Giedraitis, Vincent Deramecourt, Wolfgang Maier, Xueqiu Jian, Yolande A. L. Pijnenburg, A. David Smith, C. Abdelnour, A. D. Adarmes-Gomez, C. Macleod, Iris E. Jansen, Patrick Gavin Kehoe, Guillermo Garcia-Ribas, Pascual Sanchez-Juan, Pau Pastor, Jordi Perez-Tur, Gerard Pinol-Ripoll, Adolfo Lopez de Munain, Jose Maria Garcia-Alberca, Maria J. Bullido, Victoria Alvarez, Alberto Lleo, Luis M. Real, Pablo Mir, Miguel Medina, Philip Scheltens, Henne Holstege, Marta Marquie, Maria Eugenia Saez, Angel Carracedo, Philippe Amouyel, Gerard D. Schellenberg, Julie Williams, Sudha Seshadri, Cornelia M. van Duijn, Karen A. Mather, Raquel Sanchez-Valle, Manuel Serrano-Rios, Adelina Orellana, Lluis Tarraga, Kaj Blennow, Martijn Huisman, Ole A. Andreassen, Danielle Posthuma, Jordi Clarimon, Merce Boada, Wiesje M. van der Flier, Alfredo Ramirez, Jean-Charles Lambert, Sven J. van der Lee, Agustin Ruiz
Summary: This study identified 6 new genetic variants associated with Alzheimer's disease risk through a large-scale genetic association study. It also demonstrated the efficacy of a polygenic risk score in stratifying individuals at high risk of Alzheimer's disease, providing important data support for further research and preventive treatment of the disease.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Megan Torvell, Sarah M. Carpanini, Nikoleta Daskoulidou, Robert A. J. Byrne, Rebecca Sims, B. Paul Morgan
Summary: The pivotal role of complement activation in AD has been well studied, with genetic variations contributing significant effects on the disease. While several complement genes have been identified in association with AD, the complexity of the complement pathway poses challenges in attributing their role in disease mechanisms.
Article
Biochemistry & Molecular Biology
Karen Crawford, Ganna Leonenko, Emily Baker, Detelina Grozeva, Benoit Lan-Leung, Peter Holmans, Julie Williams, Michael C. O'Donovan, Valentina Escott-Price, Dobril K. Ivanov
Summary: Polygenic risk scores (PRS) are widely used to measure common variant liability and predict the risk of Alzheimer's disease (AD) development. This study analyzed the differential gene expression and disrupted biological pathways in AD cases, controls, and PRS using human brain-derived samples. The results revealed already implicated mechanisms and identified new processes. Glia and microglia-related terms were significantly disrupted. The findings suggest that PRS stratification can be used when suitable case/control samples are not available or in clinical trials.
MOLECULAR PSYCHIATRY
(2023)
Article
Genetics & Heredity
Henne Holstege, Marc Hulsman, Camille Charbonnier, Benjamin Grenier-Boley, Olivier Quenez, Detelina Grozeva, Jeroen G. J. van Rooij, Rebecca Sims, Shahzad Ahmad, Najaf Amin, Penny J. Norsworthy, Oriol Dols-Icardo, Holger Hummerich, Amit Kawalia, Philippe Amouyel, Gary W. Beecham, Claudine Berr, Joshua C. Bis, Anne Boland, Paola Bossu, Femke Bouwman, Jose Bras, Dominique Campion, J. Nicholas Cochran, Antonio Daniele, Jean-Francois Dartigues, Stephanie Debette, Jean-Francois Deleuze, Nicola Denning, Anita L. DeStefano, Lindsay A. Farrer, Maria Victoria Fernandez, Nick C. Fox, Daniela Galimberti, Emmanuelle Genin, Johan J. P. Gille, Yann Le Guen, Rita Guerreiro, Jonathan L. Haines, Clive Holmes, M. Arfan Ikram, M. Kamran Ikram, Iris E. Jansen, Robert Kraaij, Marc Lathrop, Afina W. Lemstra, Alberto Lleo, Lauren Luckcuck, Marcel M. A. M. Mannens, Rachel Marshall, Eden R. Martin, Carlo Masullo, Richard Mayeux, Patrizia Mecocci, Alun Meggy, Merel O. Mol, Kevin Morgan, Richard M. Myers, Benedetta Nacmias, Adam C. Naj, Valerio Napolioni, Florence Pasquier, Pau Pastor, Margaret A. Pericak-Vance, Rachel Raybould, Richard Redon, Marcel J. T. Reinders, Anne-Claire Richard, Steffi G. Riedel-Heller, Fernando Rivadeneira, Stephane Rousseau, Natalie S. Ryan, Salha Saad, Pascual Sanchez-Juan, Gerard D. Schellenberg, Philip Scheltens, Jonathan M. Schott, Davide Seripa, Sudha Seshadri, Daoud Sie, Erik A. Sistermans, Sandro Sorbi, Resie van Spaendonk, Gianfranco Spalletta, Niccolo' Tesi, Betty Tijms, Andre G. Uitterlinden, Sven J. van der Lee, Pieter Jelle Visser, Michael Wagner, David Wallon, Li-San Wang, Aline Zarea, Jordi Clarimon, John C. van Swieten, Michael D. Greicius, Jennifer S. Yokoyama, Carlos Cruchaga, John Hardy, Alfredo Ramirez, Simon Mead, Wiesje M. van der Flier, Cornelia M. van Duijn, Julie Williams, Gael Nicolas, Celine Bellenguez, Jean-Charles Lambert
Summary: Rare damaging variants in ATP8B4 and ABCA1 are significantly associated with Alzheimer's disease (AD) risk, along with a suggestive signal in ADAM10. Furthermore, genes RIN3, CLU, ZCWPW1, and ACE are potential drivers of AD-genome-wide association study loci. Loss-of-function variants, particularly in early-onset AD cases, seem to have the strongest effect on AD risk. Our findings provide additional evidence for the involvement of amyloid-beta precursor protein processing, amyloid-beta aggregation, lipid metabolism, and microglial function in AD.
Article
Clinical Neurology
Janet C. Harwood, Ganna Leonenko, Rebecca Sims, Valentina Escott-Price, Julie Williams, Peter Holmans
Summary: Alzheimer's disease is a complex polygenic disorder with most genetic variants being non-coding, influencing gene expression through various mechanisms. Transcriptome-wide association studies help to test the genetic association between disease risk and cell/tissue-specific gene expression.
BRAIN COMMUNICATIONS
(2021)
Article
Cell Biology
Laura Madrid, Sonia Moreno-Grau, Shahzad Ahmad, Antonio Gonzalez-Perez, Itziar de Rojas, Rui Xia, Pamela V. Martino Adami, Pabio Garcia-Gonzalez, Luca Kleineidam, Qiong Yang, Vincent Damotte, Joshua C. Bis, Fuensanta Noguera-Perea, Celine Bellenguez, Xueqiu Jian, Juan Marin-Munoz, Benjamin Grenier-Boley, Adela Orellana, M. Arfan Ikram, Philippe Amouyel, Claudia L. Satizabal, Luis Miguel Real, Carmen Antunez-Almagro, Anita DeStefano, Alfredo Cabrera-Socorro, Rebecca Sims, Cornelia M. Van Duijn, Eric Boerwinkle, Alfredo Ramirez, Myriam Fornage, Jean-Charles Lambert, Julie Williams, Sudha Seshadri, Janina S. Ried, Agustin Ruiz, Maria Eugenia Saez
Summary: The study analyzed publicly available data of multiple OMICS technologies from both plasma and brain stratified by APOE haplotype and identified genes and pathways contributing to AD. They also identified a set of biomarkers that could serve as screening tools for a disease lacking specific blood biomarkers.