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2. The genetic landscape of neuro-related proteins in human plasma

Author

Repetto, Linda, Chen, Jiantao, Yang, Zhijian, Zhai, Ranran, Timmers, Paul R. H. J., Feng, Xiao, Li, Ting, Yao, Yue, Maslov, Denis, Timoshchuk, Anna, Tu, Fengyu, Twait, Emma L., May-Wilson, Sebastian, Muckian, Marisa D., Prins, Bram P., Png, Grace, Kooperberg, Charles, Johansson, Åsa, Hillary, Robert F., Wheeler, Eleanor, Pan, Lu, He, Yazhou, Klasson, Sofia, Ahmad, Shahzad, Peters, James E., Gilly, Arthur, Karaleftheri, Maria, Tsafantakis, Emmanouil, Haessler, Jeffrey, Gyllensten, Ulf, Harris, Sarah E., Wareham, Nicholas J., Göteson, Andreas, Lagging, Cecilia, Ikram, Mohammad Arfan, van Duijn, Cornelia M., Jern, Christina, Landén, Mikael, Langenberg, Claudia, Deary, Ian J., Marioni, Riccardo E., Enroth, Stefan, Reiner, Alexander P., Dedoussis, George, Zeggini, Eleftheria, Sharapov, Sodbo, Aulchenko, Yurii S., Butterworth, Adam S., Mälarstig, Anders, Wilson, James F., Navarro, Pau, and Shen, Xia

Published
2024
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6. Predicting Traffic Flow with Federated Learning and Graph Neural with Asynchronous Computations Network

Author

Yaqub, Muhammad, Ahmad, Shahzad, Manan, Malik Abdul, and Chuhan, Imran Shabir

Subjects
Computer Science - Machine Learning, Computer Science - Computer Vision and Pattern Recognition
Abstract

Real-time traffic flow prediction holds significant importance within the domain of Intelligent Transportation Systems (ITS). The task of achieving a balance between prediction precision and computational efficiency presents a significant challenge. In this article, we present a novel deep-learning method called Federated Learning and Asynchronous Graph Convolutional Network (FLAGCN). Our framework incorporates the principles of asynchronous graph convolutional networks with federated learning to enhance the accuracy and efficiency of real-time traffic flow prediction. The FLAGCN model employs a spatial-temporal graph convolution technique to asynchronously address spatio-temporal dependencies within traffic data effectively. To efficiently handle the computational requirements associated with this deep learning model, this study used a graph federated learning technique known as GraphFL. This approach is designed to facilitate the training process. The experimental results obtained from conducting tests on two distinct traffic datasets demonstrate that the utilization of FLAGCN leads to the optimization of both training and inference durations while maintaining a high level of prediction accuracy. FLAGCN outperforms existing models with significant improvements by achieving up to approximately 6.85% reduction in RMSE, 20.45% reduction in MAPE, compared to the best-performing existing models., Comment: I request to withdraw my paper from arXiv due to significant updates and improvements identified post-submission. These enhancements will substantially elevate the work's quality and impact. I plan to resubmit the revised paper upon completion of these updates. Thank you for accommodating this request

Published
2024

7. EZ-CLIP: Efficient Zeroshot Video Action Recognition

Author

Ahmad, Shahzad, Chanda, Sukalpa, and Rawat, Yogesh S

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

Recent advancements in large-scale pre-training of visual-language models on paired image-text data have demonstrated impressive generalization capabilities for zero-shot tasks. Building on this success, efforts have been made to adapt these image-based visual-language models, such as CLIP, for videos extending their zero-shot capabilities to the video domain. While these adaptations have shown promising results, they come at a significant computational cost and struggle with effectively modeling the crucial temporal aspects inherent to the video domain. In this study, we present EZ-CLIP, a simple and efficient adaptation of CLIP that addresses these challenges. EZ-CLIP leverages temporal visual prompting for seamless temporal adaptation, requiring no fundamental alterations to the core CLIP architecture while preserving its remarkable generalization abilities. Moreover, we introduce a novel learning objective that guides the temporal visual prompts to focus on capturing motion, thereby enhancing its learning capabilities from video data. We conducted extensive experiments on five different benchmark datasets, thoroughly evaluating EZ-CLIP for zero-shot learning and base-to-novel video action recognition, and also demonstrating its potential for few-shot generalization.Impressively, with a mere 5.2 million learnable parameters (as opposed to the 71.1 million in the prior best model), EZ-CLIP can be efficiently trained on a single GPU, outperforming existing approaches in several evaluations.

Published
2023

10. Genome-wide association study meta-analysis of neurofilament light (NfL) levels in blood reveals novel loci related to neurodegeneration

Author

Ahmad, Shahzad, Imtiaz, Mohammad Aslam, Mishra, Aniket, Wang, Ruiqi, Herrera-Rivero, Marisol, Bis, Joshua C, Fornage, Myriam, Roshchupkin, Gennady, Hofer, Edith, Logue, Mark, Longstreth, WT, Xia, Rui, Bouteloup, Vincent, Mosley, Thomas, Launer, Lenore J, Khalil, Michael, Kuhle, Jens, Rissman, Robert A, Chene, Genevieve, Dufouil, Carole, Djoussé, Luc, Lyons, Michael J, Mukamal, Kenneth J, Kremen, William S, Franz, Carol E, Schmidt, Reinhold, Debette, Stephanie, Breteler, Monique MB, Berger, Klaus, Yang, Qiong, Seshadri, Sudha, Aziz, N Ahmad, Ghanbari, Mohsen, and Ikram, M Arfan

Subjects
Biological Sciences, Genetics, Neurodegenerative, Acquired Cognitive Impairment, Human Genome, Dementia, Neurosciences, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Prevention, Aging, 2.1 Biological and endogenous factors, Neurological, Humans, Genome-Wide Association Study, Neurofilament Proteins, Neurodegenerative Diseases, Genetic Predisposition to Disease, Genetic Loci, Biomarkers, Polymorphism, Single Nucleotide, Male, Female, Alzheimer Disease, Biological sciences, Biomedical and clinical sciences
Abstract

Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify three additional genome-wide significant loci at 1p32 (FGGY), 6q14 (TBX18), and 4q21. In the post-GWAS analyses, we observe the association of higher NfL polygenic risk score with increased plasma levels of total-tau, Aβ-40, Aβ-42, and higher incidence of Alzheimer's disease in the Rotterdam Study. Furthermore, Mendelian randomization analysis results suggest that a lower kidney function could cause higher blood NfL levels. This study uncovers multiple genetic loci of blood NfL levels, highlighting the genes related to molecular mechanism of neurodegeneration.

Published
2024

11. A Type 1 Diabetes Polygenic Score Is Not Associated With Prevalent Type 2 Diabetes in Large Population Studies

Author

Srinivasan, Shylaja, Wu, Peitao, Mercader, Josep M, Udler, Miriam S, Porneala, Bianca C, Bartz, Traci M, Floyd, James S, Sitlani, Colleen, Guo, Xiquing, Haessler, Jeffrey, Kooperberg, Charles, Liu, Jun, Ahmad, Shahzad, van Duijn, Cornelia, Liu, Ching-Ti, Goodarzi, Mark O, Florez, Jose C, Meigs, James B, Rotter, Jerome I, Rich, Stephen S, Dupuis, Josée, and Leong, Aaron

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Diabetes, Pediatric, Genetics, Autoimmune Disease, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, type 1 diabetes, type 2 diabetes, genetics, polygenic score, Cardiovascular medicine and haematology
Abstract

ContextBoth type 1 diabetes (T1D) and type 2 diabetes (T2D) have significant genetic contributions to risk and understanding their overlap can offer clinical insight.ObjectiveWe examined whether a T1D polygenic score (PS) was associated with a diagnosis of T2D in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.MethodsWe constructed a T1D PS using 79 known single nucleotide polymorphisms associated with T1D risk. We analyzed 13 792 T2D cases and 14 169 controls from CHARGE cohorts to determine the association between the T1D PS and T2D prevalence. We validated findings in an independent sample of 2256 T2D cases and 27 052 controls from the Mass General Brigham Biobank (MGB Biobank). As secondary analyses in 5228 T2D cases from CHARGE, we used multivariable regression models to assess the association of the T1D PS with clinical outcomes associated with T1D.ResultsThe T1D PS was not associated with T2D both in CHARGE (P = .15) and in the MGB Biobank (P = .87). The partitioned human leukocyte antigens only PS was associated with T2D in CHARGE (OR 1.02 per 1 SD increase in PS, 95% CI 1.01-1.03, P = .006) but not in the MGB Biobank. The T1D PS was weakly associated with insulin use (OR 1.007, 95% CI 1.001-1.012, P = .03) in CHARGE T2D cases but not with other outcomes.ConclusionIn large biobank samples, a common variant PS for T1D was not consistently associated with prevalent T2D. However, possible heterogeneity in T2D cannot be ruled out and future studies are needed do subphenotyping.

Published
2023

12. Association of oxidative stress and inflammatory metabolites with Alzheimer’s disease cerebrospinal fluid biomarkers in mild cognitive impairment

Author

Ahmad, Shahzad, Yang, Wei, Orellana, Adelina, Frölich, Lutz, de Rojas, Itziar, Cano, Amanda, Boada, Mercè, Hernández, Isabel, Hausner, Lucrezia, Harms, Amy C., Bakker, Margot H. M., Cabrera-Socorro, Alfredo, Amin, Najaf, Ramírez, Alfredo, Ruiz, Agustín, Van Duijn, Cornelia M., and Hankemeier, Thomas

Published
2024
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15. Metricizing the Euclidean Space towards Desired Distance Relations in Point Clouds

Author

Rass, Stefan, König, Sandra, Ahmad, Shahzad, and Goman, Maksim

Subjects
Computer Science - Computational Geometry, Computer Science - Machine Learning
Abstract

Given a set of points in the Euclidean space $\mathbb{R}^\ell$ with $\ell>1$, the pairwise distances between the points are determined by their spatial location and the metric $d$ that we endow $\mathbb{R}^\ell$ with. Hence, the distance $d(\mathbf x,\mathbf y)=\delta$ between two points is fixed by the choice of $\mathbf x$ and $\mathbf y$ and $d$. We study the related problem of fixing the value $\delta$, and the points $\mathbf x,\mathbf y$, and ask if there is a topological metric $d$ that computes the desired distance $\delta$. We demonstrate this problem to be solvable by constructing a metric to simultaneously give desired pairwise distances between up to $O(\sqrt\ell)$ many points in $\mathbb{R}^\ell$. We then introduce the notion of an $\varepsilon$-semimetric $\tilde{d}$ to formulate our main result: for all $\varepsilon>0$, for all $m\geq 1$, for any choice of $m$ points $\mathbf y_1,\ldots,\mathbf y_m\in\mathbb{R}^\ell$, and all chosen sets of values $\{\delta_{ij}\geq 0: 1\leq i

Published
2022
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19. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease

Author

Holstege, Henne, Hulsman, Marc, Charbonnier, Camille, Grenier-Boley, Benjamin, Quenez, Olivier, Grozeva, Detelina, van Rooij, Jeroen GJ, Sims, Rebecca, Ahmad, Shahzad, Amin, Najaf, Norsworthy, Penny J, Dols-Icardo, Oriol, Hummerich, Holger, Kawalia, Amit, Amouyel, Philippe, Beecham, Gary W, Berr, Claudine, Bis, Joshua C, Boland, Anne, Bossù, Paola, Bouwman, Femke, Bras, Jose, Campion, Dominique, Cochran, J Nicholas, Daniele, Antonio, Dartigues, Jean-François, Debette, Stéphanie, Deleuze, Jean-François, Denning, Nicola, DeStefano, Anita L, Farrer, Lindsay A, Fernández, Maria Victoria, Fox, Nick C, Galimberti, Daniela, Genin, Emmanuelle, Gille, Johan JP, Le Guen, Yann, Guerreiro, Rita, Haines, Jonathan L, Holmes, Clive, Ikram, M Arfan, Ikram, M Kamran, Jansen, Iris E, Kraaij, Robert, Lathrop, Marc, Lemstra, Afina W, Lleó, Alberto, Luckcuck, Lauren, Mannens, Marcel MAM, Marshall, Rachel, Martin, Eden R, Masullo, Carlo, Mayeux, Richard, Mecocci, Patrizia, Meggy, Alun, Mol, Merel O, Morgan, Kevin, Myers, Richard M, Nacmias, Benedetta, Naj, Adam C, Napolioni, Valerio, Pasquier, Florence, Pastor, Pau, Pericak-Vance, Margaret A, Raybould, Rachel, Redon, Richard, Reinders, Marcel JT, Richard, Anne-Claire, Riedel-Heller, Steffi G, Rivadeneira, Fernando, Rousseau, Stéphane, Ryan, Natalie S, Saad, Salha, Sanchez-Juan, Pascual, Schellenberg, Gerard D, Scheltens, Philip, Schott, Jonathan M, Seripa, Davide, Seshadri, Sudha, Sie, Daoud, Sistermans, Erik A, Sorbi, Sandro, van Spaendonk, Resie, Spalletta, Gianfranco, Tesi, Niccolo’, Tijms, Betty, Uitterlinden, André G, van der Lee, Sven J, Visser, Pieter Jelle, Wagner, Michael, Wallon, David, Wang, Li-San, Zarea, Aline, Clarimon, Jordi, van Swieten, John C, Greicius, Michael D, Yokoyama, Jennifer S, Cruchaga, Carlos, Hardy, John, and Ramirez, Alfredo

Subjects
Biological Sciences, Genetics, Dementia, Alzheimer's Disease, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Prevention, Acquired Cognitive Impairment, Neurodegenerative, Aging, Clinical Research, Biotechnology, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Humans, Adenosine Triphosphatases, Alzheimer Disease, ATP Binding Cassette Transporter 1, Genome-Wide Association Study, Risk Factors, Exosomes, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.

Published
2022

22. Contributors

Author

Abhilash, T.K., primary, Ahmad, Shahzad, additional, Ahmad, Towseef, additional, Alvarez-Contreras, Lorena, additional, Anas, S., additional, Ansari, Mohd Zubair, additional, Arjona, Noé, additional, Asok, Adersh, additional, Ayoub, Irfan, additional, Azeem, P. Abdul, additional, Chandran, Achu, additional, Chauhan, Vishnu, additional, Coetsee, E., additional, De, Ranjit, additional, Díaz-Real, Jesús Adrián, additional, Divya, J., additional, Fernandes, Jean Maria, additional, González-Nava, Catalina, additional, Guerra-Balcázar, Minerva, additional, Gupta, Deepika, additional, Gupta, Swadesh Kumar, additional, Joseph, D. Paul, additional, Kaur, Harjot, additional, Kovendhan, M., additional, Kulkarni, Ajit R., additional, Kumar, Pragati, additional, Kumar, Rajesh, additional, Kumar, Vijay, additional, Kumari, Anita, additional, M.S., Sangeetha, additional, Mahata, Manoj Kumar, additional, Mishra, Sanjeev Kumar, additional, Mushtaq, Umer, additional, Oguzlar, Sibel, additional, Ramachandran, Animesh M., additional, Sarkar, Sayoni, additional, Saxena, Nupur, additional, Shah, Asmita, additional, Sharma, Savita, additional, Sharma, Vishal, additional, Shivaramu, N.J., additional, Singh, Dharmendra Pratap, additional, Singh, Manjit, additional, Singh, Narinder, additional, Sinha, Shriya, additional, Siwal, Samarjeet Singh, additional, Swart, Hendrik C., additional, Taunk, Manish, additional, Thampi, Adhithya S., additional, Tyagi, Jyoti, additional, Upadhyay, Sonica, additional, Varghese, Harris, additional, Vashisht, Garima, additional, Yadav, Pooja, additional, Yagoub, M.Y.A., additional, and Zeyrek Ongun, Merve, additional

Published
2024
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23. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author

Lahti, Jari, Tuominen, Samuli, Yang, Qiong, Pergola, Giulio, Ahmad, Shahzad, Amin, Najaf, Armstrong, Nicola J, Beiser, Alexa, Bey, Katharina, Bis, Joshua C, Boerwinkle, Eric, Bressler, Jan, Campbell, Archie, Campbell, Harry, Chen, Qiang, Corley, Janie, Cox, Simon R, Davies, Gail, De Jager, Philip L, Derks, Eske M, Faul, Jessica D, Fitzpatrick, Annette L, Fohner, Alison E, Ford, Ian, Fornage, Myriam, Gerring, Zachary, Grabe, Hans J, Grodstein, Francine, Gudnason, Vilmundur, Simonsick, Eleanor, Holliday, Elizabeth G, Joshi, Peter K, Kajantie, Eero, Kaprio, Jaakko, Karell, Pauliina, Kleineidam, Luca, Knol, Maria J, Kochan, Nicole A, Kwok, John B, Leber, Markus, Lam, Max, Lee, Teresa, Li, Shuo, Loukola, Anu, Luck, Tobias, Marioni, Riccardo E, Mather, Karen A, Medland, Sarah, Mirza, Saira S, Nalls, Mike A, Nho, Kwangsik, O’Donnell, Adrienne, Oldmeadow, Christopher, Painter, Jodie, Pattie, Alison, Reppermund, Simone, Risacher, Shannon L, Rose, Richard J, Sadashivaiah, Vijay, Scholz, Markus, Satizabal, Claudia L, Schofield, Peter W, Schraut, Katharina E, Scott, Rodney J, Simino, Jeannette, Smith, Albert V, Smith, Jennifer A, Stott, David J, Surakka, Ida, Teumer, Alexander, Thalamuthu, Anbupalam, Trompet, Stella, Turner, Stephen T, van der Lee, Sven J, Villringer, Arno, Völker, Uwe, Wilson, Robert S, Wittfeld, Katharina, Vuoksimaa, Eero, Xia, Rui, Yaffe, Kristine, Yu, Lei, Zare, Habil, Zhao, Wei, Ames, David, Attia, John, Bennett, David A, Brodaty, Henry, Chasman, Daniel I, Goldman, Aaron L, Hayward, Caroline, Ikram, M Arfan, Jukema, J Wouter, Kardia, Sharon LR, Lencz, Todd, Loeffler, Markus, Mattay, Venkata S, Palotie, Aarno, Psaty, Bruce M, and Ramirez, Alfredo

Subjects
Biological Psychology, Psychology, Genetics, Human Genome, Dementia, Behavioral and Social Science, Brain Disorders, Acquired Cognitive Impairment, Mental Health, Biotechnology, Aging, Clinical Research, Neurosciences, Basic Behavioral and Social Science, Aetiology, 2.1 Biological and endogenous factors, Neurological, Mental health, Memory, Short-Term, Learning, Verbal Learning, Multifactorial Inheritance, Brain, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

Published
2022

25. Circulating Metabolome and White Matter Hyperintensities in Women and Men

Author

Sliz, Eeva, Shin, Jean, Ahmad, Shahzad, Williams, Dylan M, Frenzel, Stefan, Gauß, Friederike, Harris, Sarah E, Henning, Ann-Kristin, Hernandez, Maria Valdes, Hu, Yi-Han, Jiménez, Beatriz, Sargurupremraj, Muralidharan, Sudre, Carole, Wang, Ruiqi, Wittfeld, Katharina, Yang, Qiong, Wardlaw, Joanna M, Völzke, Henry, Vernooij, Meike W, Schott, Jonathan M, Richards, Marcus, Proitsi, Petroula, Nauck, Matthias, Lewis, Matthew R, Launer, Lenore, Hosten, Norbert, Grabe, Hans J, Ghanbari, Mohsen, Deary, Ian J, Cox, Simon R, Chaturvedi, Nishi, Barnes, Josephine, Rotter, Jerome I, Debette, Stephanie, Ikram, M Arfan, Fornage, Myriam, Paus, Tomas, Seshadri, Sudha, Pausova, Zdenka, and Group, for the NeuroCHARGE Working

Subjects
Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Prevention, Clinical Research, Aging, Aged, Brain, Diabetes Mellitus, Type 2, Female, Humans, Magnetic Resonance Imaging, Male, Metabolome, Middle Aged, White Matter, NeuroCHARGE Working Group, brain, glucuronic acid, hydroxyphenylpyruvate, lipid ratios, lipidomics, lipids, lysophosphatidylcholines, metabolomics, sphingomyelins, white matter, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Sports science and exercise
Abstract

BackgroundWhite matter hyperintensities (WMH), identified on T2-weighted magnetic resonance images of the human brain as areas of enhanced brightness, are a major risk factor of stroke, dementia, and death. There are no large-scale studies testing associations between WMH and circulating metabolites.MethodsWe studied up to 9290 individuals (50.7% female, average age 61 years) from 15 populations of 8 community-based cohorts. WMH volume was quantified from T2-weighted or fluid-attenuated inversion recovery images or as hypointensities on T1-weighted images. Circulating metabolomic measures were assessed with mass spectrometry and nuclear magnetic resonance spectroscopy. Associations between WMH and metabolomic measures were tested by fitting linear regression models in the pooled sample and in sex-stratified and statin treatment-stratified subsamples. Our basic models were adjusted for age, sex, age×sex, and technical covariates, and our fully adjusted models were also adjusted for statin treatment, hypertension, type 2 diabetes, smoking, body mass index, and estimated glomerular filtration rate. Population-specific results were meta-analyzed using the fixed-effect inverse variance-weighted method. Associations with false discovery rate (FDR)-adjusted P values (PFDR)

Published
2022

26. New insights into the genetic etiology of Alzheimer’s disease and related dementias

Author

Bellenguez, Céline, Küçükali, Fahri, Jansen, Iris E, Kleineidam, Luca, Moreno-Grau, Sonia, Amin, Najaf, Naj, Adam C, Campos-Martin, Rafael, Grenier-Boley, Benjamin, Andrade, Victor, Holmans, Peter A, Boland, Anne, Damotte, Vincent, van der Lee, Sven J, Costa, Marcos R, Kuulasmaa, Teemu, Yang, Qiong, de Rojas, Itziar, Bis, Joshua C, Yaqub, Amber, Prokic, Ivana, Chapuis, Julien, Ahmad, Shahzad, Giedraitis, Vilmantas, Aarsland, Dag, Garcia-Gonzalez, Pablo, Abdelnour, Carla, Alarcón-Martín, Emilio, Alcolea, Daniel, Alegret, Montserrat, Alvarez, Ignacio, Álvarez, Victoria, Armstrong, Nicola J, Tsolaki, Anthoula, Antúnez, Carmen, Appollonio, Ildebrando, Arcaro, Marina, Archetti, Silvana, Pastor, Alfonso Arias, Arosio, Beatrice, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa, Baquero, Miquel, Barral, Sandra, Beiser, Alexa, Pastor, Ana Belén, Below, Jennifer E, Benchek, Penelope, Benussi, Luisa, Berr, Claudine, Besse, Céline, Bessi, Valentina, Binetti, Giuliano, Bizarro, Alessandra, Blesa, Rafael, Boada, Mercè, Boerwinkle, Eric, Borroni, Barbara, Boschi, Silvia, Bossù, Paola, Bråthen, Geir, Bressler, Jan, Bresner, Catherine, Brodaty, Henry, Brookes, Keeley J, Brusco, Luis Ignacio, Buiza-Rueda, Dolores, Bûrger, Katharina, Burholt, Vanessa, Bush, William S, Calero, Miguel, Cantwell, Laura B, Chene, Geneviève, Chung, Jaeyoon, Cuccaro, Michael L, Carracedo, Ángel, Cecchetti, Roberta, Cervera-Carles, Laura, Charbonnier, Camille, Chen, Hung-Hsin, Chillotti, Caterina, Ciccone, Simona, Claassen, Jurgen AHR, Clark, Christopher, Conti, Elisa, Corma-Gómez, Anaïs, Costantini, Emanuele, Custodero, Carlo, Daian, Delphine, Dalmasso, Maria Carolina, Daniele, Antonio, Dardiotis, Efthimios, Dartigues, Jean-François, de Deyn, Peter Paul, de Paiva Lopes, Katia, de Witte, Lot D, Debette, Stéphanie, Deckert, Jürgen, and del Ser, Teodoro

Subjects
Biochemistry and Cell Biology, Genetics, Biological Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Neurodegenerative, Alzheimer's Disease, Human Genome, Prevention, Aging, Brain Disorders, Acquired Cognitive Impairment, Neurosciences, Genetic Testing, 2.1 Biological and endogenous factors, Aetiology, Neurological, Alzheimer Disease, Cognitive Dysfunction, Genome-Wide Association Study, Humans, tau Proteins, EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

Published
2022

28. Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels

Author

Sarnowski, Chloé, Ghanbari, Mohsen, Bis, Joshua C, Logue, Mark, Fornage, Myriam, Mishra, Aniket, Ahmad, Shahzad, Beiser, Alexa S, Boerwinkle, Eric, Bouteloup, Vincent, Chouraki, Vincent, Cupples, L Adrienne, Damotte, Vincent, DeCarli, Charles S, DeStefano, Anita L, Djoussé, Luc, Fohner, Alison E, Franz, Carol E, Kautz, Tiffany F, Lambert, Jean-Charles, Lyons, Michael J, Mosley, Thomas H, Mukamal, Kenneth J, Pase, Matthew P, Portilla Fernandez, Eliana C, Rissman, Robert A, Satizabal, Claudia L, Vasan, Ramachandran S, Yaqub, Amber, Debette, Stephanie, Dufouil, Carole, Launer, Lenore J, Kremen, William S, Longstreth, William T, Ikram, M Arfan, and Seshadri, Sudha

Subjects
Biological Sciences, Genetics, Aging, Neurosciences, Neurodegenerative, Alzheimer's Disease, Dementia, Brain Disorders, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aetiology, 2.1 Biological and endogenous factors, Neurological, Black or African American, Alzheimer Disease, Exome, Genome-Wide Association Study, Humans, Tauopathies, Biological sciences, Biomedical and clinical sciences
Abstract

Circulating total-tau levels can be used as an endophenotype to identify genetic risk factors for tauopathies and related neurological disorders. Here, we confirmed and better characterized the association of the 17q21 MAPT locus with circulating total-tau in 14,721 European participants and identified three novel loci in 953 African American participants (4q31, 5p13, and 6q25) at P

Published
2022

36. Localization of Unmanned Aerial Vehicles in Corridor Environments using Deep Learning

Author

Padhy, Ram Prasad, Ahmad, Shahzad, Verma, Sachin, Sa, Pankaj Kumar, and Bakshi, Sambit

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Vision-based pose estimation of Unmanned Aerial Vehicles (UAV) in unknown environments is a rapidly growing research area in the field of robot vision. The task becomes more complex when the only available sensor is a static single camera (monocular vision). In this regard, we propose a monocular vision assisted localization algorithm, that will help a UAV to navigate safely in indoor corridor environments. Always, the aim is to navigate the UAV through a corridor in the forward direction by keeping it at the center with no orientation either to the left or right side. The algorithm makes use of the RGB image, captured from the UAV front camera, and passes it through a trained deep neural network (DNN) to predict the position of the UAV as either on the left or center or right side of the corridor. Depending upon the divergence of the UAV with respect to the central bisector line (CBL) of the corridor, a suitable command is generated to bring the UAV to the center. When the UAV is at the center of the corridor, a new image is passed through another trained DNN to predict the orientation of the UAV with respect to the CBL of the corridor. If the UAV is either left or right tilted, an appropriate command is generated to rectify the orientation. We also propose a new corridor dataset, named NITRCorrV1, which contains images as captured by the UAV front camera when the UAV is at all possible locations of a variety of corridors. An exhaustive set of experiments in different corridors reveal the efficacy of the proposed algorithm., Comment: 9 pages, 7 figures

Published
2019

37. Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.

Author

Hofer, Edith, Roshchupkin, Gennady V, Adams, Hieab HH, Knol, Maria J, Lin, Honghuang, Li, Shuo, Zare, Habil, Ahmad, Shahzad, Armstrong, Nicola J, Satizabal, Claudia L, Bernard, Manon, Bis, Joshua C, Gillespie, Nathan A, Luciano, Michelle, Mishra, Aniket, Scholz, Markus, Teumer, Alexander, Xia, Rui, Jian, Xueqiu, Mosley, Thomas H, Saba, Yasaman, Pirpamer, Lukas, Seiler, Stephan, Becker, James T, Carmichael, Owen, Rotter, Jerome I, Psaty, Bruce M, Lopez, Oscar L, Amin, Najaf, van der Lee, Sven J, Yang, Qiong, Himali, Jayandra J, Maillard, Pauline, Beiser, Alexa S, DeCarli, Charles, Karama, Sherif, Lewis, Lindsay, Harris, Mat, Bastin, Mark E, Deary, Ian J, Veronica Witte, A, Beyer, Frauke, Loeffler, Markus, Mather, Karen A, Schofield, Peter R, Thalamuthu, Anbupalam, Kwok, John B, Wright, Margaret J, Ames, David, Trollor, Julian, Jiang, Jiyang, Brodaty, Henry, Wen, Wei, Vernooij, Meike W, Hofman, Albert, Uitterlinden, André G, Niessen, Wiro J, Wittfeld, Katharina, Bülow, Robin, Völker, Uwe, Pausova, Zdenka, Bruce Pike, G, Maingault, Sophie, Crivello, Fabrice, Tzourio, Christophe, Amouyel, Philippe, Mazoyer, Bernard, Neale, Michael C, Franz, Carol E, Lyons, Michael J, Panizzon, Matthew S, Andreassen, Ole A, Dale, Anders M, Logue, Mark, Grasby, Katrina L, Jahanshad, Neda, Painter, Jodie N, Colodro-Conde, Lucía, Bralten, Janita, Hibar, Derrek P, Lind, Penelope A, Pizzagalli, Fabrizio, Stein, Jason L, Thompson, Paul M, Medland, Sarah E, ENIGMA consortium, Sachdev, Perminder S, Kremen, William S, Wardlaw, Joanna M, Villringer, Arno, van Duijn, Cornelia M, Grabe, Hans J, Longstreth, William T, Fornage, Myriam, Paus, Tomas, Debette, Stephanie, Ikram, M Arfan, Schmidt, Helena, Schmidt, Reinhold, and Seshadri, Sudha

Subjects
ENIGMA consortium, Brain, Chromosome Structures, Humans, Neurodegenerative Diseases, Cognition, Mental Disorders, Genomics, Aging, Phenotype, Polymorphism, Single Nucleotide, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study, Genetics, Neurosciences, Human Genome, Brain Disorders, Biotechnology, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Neurological
Abstract

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

Published
2020

42. Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author

Kunkle, Brian W, Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C, Damotte, Vincent, Naj, Adam C, Boland, Anne, Vronskaya, Maria, van der Lee, Sven J, Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R, Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L, Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B, Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N, Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W, Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L, Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V, Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C, Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T, Adams, Hieab H, Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A, Dombroski, Beth A, Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B, Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S, Meslage, Stéphane, Kornhuber, Johannes, White, Charles C, Song, Yuenjoo, Barber, Robert C, Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M, Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L Adrienne, Albert, Marilyn S, De Deyn, Peter P, Gu, Wei, Himali, Jayanadra J, Beekly, Duane, Squassina, Alessio, Hartmann, Annette M, Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E, Doody, Rachelle S, Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J, and Benito, Yolanda A

Subjects
Biochemistry and Cell Biology, Biological Sciences, Alzheimer Disease Genetics Consortium, European Alzheimer’s Disease Initiative, Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology, Genetics
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

43. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author

Kunkle, Brian W, Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C, Damotte, Vincent, Naj, Adam C, Boland, Anne, Vronskaya, Maria, van der Lee, Sven J, Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R, Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L, Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B, Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N, Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W, Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L, Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V, Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C, Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T, Adams, Hieab H, Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A, Dombroski, Beth A, Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B, Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S, Meslage, Stéphane, Kornhuber, Johannes, White, Charles C, Song, Yuenjoo, Barber, Robert C, Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M, Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L Adrienne, Albert, Marilyn S, De Deyn, Peter P, Gu, Wei, Himali, Jayanadra J, Beekly, Duane, Squassina, Alessio, Hartmann, Annette M, Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E, Doody, Rachelle S, Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J, and Benito, Yolanda A

Subjects
Biochemistry and Cell Biology, Genetics, Biological Sciences, Neurodegenerative, Dementia, Alzheimer's Disease, Aging, Prevention, Brain Disorders, Neurosciences, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Neurological, Aged, Alzheimer Disease, Amyloid beta-Peptides, Case-Control Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genetic Testing, Genome-Wide Association Study, Haplotypes, Humans, Immunity, Lipid Metabolism, Lipids, Male, tau Proteins, Alzheimer Disease Genetics Consortium (ADGC), European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD/PERADES), Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.

Published
2019

44. Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers

Author

Nho, Kwangsik, Kueider‐Paisley, Alexandra, MahmoudianDehkordi, Siamak, Arnold, Matthias, Risacher, Shannon L, Louie, Gregory, Blach, Colette, Baillie, Rebecca, Han, Xianlin, Kastenmüller, Gabi, Jia, Wei, Xie, Guoxiang, Ahmad, Shahzad, Hankemeier, Thomas, van Duijn, Cornelia M, Trojanowski, John Q, Shaw, Leslie M, Weiner, Michael W, Doraiswamy, P Murali, Saykin, Andrew J, Kaddurah‐Daouk, Rima, and Consortium, for the Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Digestive Diseases, Aging, Neurosciences, Neurodegenerative, Alzheimer's Disease, Dementia, Brain Disorders, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Biomedical Imaging, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Alzheimer Disease, Amyloid beta-Peptides, Bile Acids and Salts, Biomarkers, Cognitive Dysfunction, Female, Fluorodeoxyglucose F18, Humans, Magnetic Resonance Imaging, Male, Neuroimaging, Positron-Emission Tomography, Prospective Studies, tau Proteins, Metabolomics, Bile acid, Alzheimer's disease, Amyloid-beta, CSF biomarkers, Brain glucose metabolism, PET, MRI, Gut-liver-brain axis, Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium, Amyloid-β, Clinical Sciences, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionBile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer's disease (AD) including neuroinflammation and amyloid-β deposition.MethodSerum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n = 1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the "A/T/N" (amyloid, tau, and neurodegeneration) biomarkers for AD: cerebrospinal fluid (CSF) biomarkers, atrophy (magnetic resonance imaging), and brain glucose metabolism ([18F]FDG PET).ResultsOf 23 BAs and relevant calculated ratios after quality control procedures, three BA signatures were associated with CSF Aβ1-42 ("A") and three with CSF p-tau181 ("T") (corrected P

Published
2019

45. Altered bile acid profile associates with cognitive impairment in Alzheimer's disease—An emerging role for gut microbiome

Author

MahmoudianDehkordi, Siamak, Arnold, Matthias, Nho, Kwangsik, Ahmad, Shahzad, Jia, Wei, Xie, Guoxiang, Louie, Gregory, Kueider‐Paisley, Alexandra, Moseley, M Arthur, Thompson, J Will, St John Williams, Lisa, Tenenbaum, Jessica D, Blach, Colette, Baillie, Rebecca, Han, Xianlin, Bhattacharyya, Sudeepa, Toledo, Jon B, Schafferer, Simon, Klein, Sebastian, Koal, Therese, Risacher, Shannon L, Kling, Mitchel Allan, Motsinger‐Reif, Alison, Rotroff, Daniel M, Jack, John, Hankemeier, Thomas, Bennett, David A, De Jager, Philip L, Trojanowski, John Q, Shaw, Leslie M, Weiner, Michael W, Doraiswamy, P Murali, van Duijn, Cornelia M, Saykin, Andrew J, Kastenmüller, Gabi, Kaddurah‐Daouk, Rima, and Consortium, for the Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics

Subjects
Biological Psychology, Psychology, Digestive Diseases, Aging, Neurosciences, Neurodegenerative, Alzheimer's Disease, Dementia, Brain Disorders, Acquired Cognitive Impairment, Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Behavioral and Social Science, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Alzheimer Disease, Bile Acids and Salts, Cognitive Dysfunction, Dysbiosis, Female, Gastrointestinal Microbiome, Humans, Liver, Male, Metabolome, Metabolomics, Lipidomics, Alzheimer's disease, Gut microbiome, Gut-liver-brain axis, Atlas for Alzheimer, Genetic variants, Immunity, Inflammation, Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium, Clinical Sciences, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionIncreasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut-brain axis in neurodegeneration. Bile acids (BAs), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer's disease (AD).MethodsSerum levels of 15 primary and secondary BAs and their conjugated forms were measured in 1464 subjects including 370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 with late mild cognitive impairment, and 305 AD cases enrolled in the AD Neuroimaging Initiative. We assessed associations of BA profiles including selected ratios with diagnosis, cognition, and AD-related genetic variants, adjusting for confounders and multiple testing.ResultsIn AD compared to cognitively normal older adults, we observed significantly lower serum concentrations of a primary BA (cholic acid [CA]) and increased levels of the bacterially produced, secondary BA, deoxycholic acid, and its glycine and taurine conjugated forms. An increased ratio of deoxycholic acid:CA, which reflects 7α-dehydroxylation of CA by gut bacteria, strongly associated with cognitive decline, a finding replicated in serum and brain samples in the Rush Religious Orders and Memory and Aging Project. Several genetic variants in immune response-related genes implicated in AD showed associations with BA profiles.DiscussionWe report for the first time an association between altered BA profile, genetic variants implicated in AD, and cognitive changes in disease using a large multicenter study. These findings warrant further investigation of gut dysbiosis and possible role of gut-liver-brain axis in the pathogenesis of AD.

Published
2019

48. Challenges at the APOE locus: a robust quality control approach for accurate APOE genotyping

Author

Belloy, Michael E., Eger, Sarah J., Le Guen, Yann, Damotte, Vincent, Ahmad, Shahzad, Ikram, M. Arfan, Ramirez, Alfredo, Tsolaki, Anthoula C., Rossi, Giacomina, Jansen, Iris E., de Rojas, Itziar, Parveen, Kayenat, Sleegers, Kristel, Ingelsson, Martin, Hiltunen, Mikko, Amin, Najaf, Andreassen, Ole, Sánchez-Juan, Pascual, Kehoe, Patrick, Amouyel, Philippe, Sims, Rebecca, Frikke-Schmidt, Ruth, van der Flier, Wiesje M., Lambert, Jean-Charles, He, Zihuai, Han, Summer S., Napolioni, Valerio, and Greicius, Michael D.

Published
2022
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50. A Multi-Function Novel Crop Seeder for the Management of Residues and Mechanized Sowing of Wheat in a Single Path.

Author

Yaseen, Muhammad Usama, Ahmad, Shahzad, Ahmad, Maqsood, Long, John M., Raza, Hafiz Ali, Iftekhar, Hassan, Ameer, Sikander, and Ogunbiyi, Dabira

Subjects
*CROP management, *FIELD crops, *FERTILIZER application, *CROP residues, *SPUR gearing
Abstract

The handling of the remnants of rice crops in the field is not an easy operation, and farmers prefer burning, which causes air pollution, smog, and disease. This research reports the development of a novel precision crop seeder by handling the remnants of previous crops through mechanization. The precision seeder performed multiple operations in a single path, viz, chop residues, incorporate into soil, make mini trenches, and sow wheat with fertilizer application. The precision seeder has a 2040 mm working width, and specially designed C-type blades are used to shred the crop residue. A multiple-speed gearbox with a gear ratio of 1:0.52 is installed, with a further set of spur gears with 16, 18, and 20 teeth that provide 225, 250, 310, and 350 RPMs to the main rotor. In the middle of the seeder, after the main rotor shaft, 11 V-shaped trencher plates are fixed on the trencher roller for the making of trenches. The trencher roller is powered by star wheels, which showed good results. A zero-tillage-type sharp tip edge novel seeder unit was developed for the precise placement of seed and fertilizer. Seed and fertilizer were placed into the mini trenches through 11 seeder units through a ground wheel calibration system. The field capacity of the precision seeder was 0.408 ha/h and the operational cost was calculated 40.68 USD/ha. The seeder showed good results, with the production of 5028 kg/ha compared to conventional methods. The precision seeder provides a mechanized solution for wheat sowing with minimal operational costs by enhancing organic matter in soil with 13% more yield. [ABSTRACT FROM AUTHOR]

Published
2024
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