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186 results on '"Belloy, Michael E."'

1. Robust inference with GhostKnockoffs in genome-wide association studies

Author

Qi, Xinran, Belloy, Michael E., Gu, Jiaqi, Liu, Xiaoxia, Tang, Hua, and He, Zihuai

Subjects
Statistics - Methodology
Abstract

Genome-wide association studies (GWASs) have been extensively adopted to depict the underlying genetic architecture of complex diseases. Motivated by GWASs' limitations in identifying small effect loci to understand complex traits' polygenicity and fine-mapping putative causal variants from proxy ones, we propose a knockoff-based method which only requires summary statistics from GWASs and demonstrate its validity in the presence of relatedness. We show that GhostKnockoffs inference is robust to its input Z-scores as long as they are from valid marginal association tests and their correlations are consistent with the correlations among the corresponding genetic variants. The property generalizes GhostKnockoffs to other GWASs settings, such as the meta-analysis of multiple overlapping studies and studies based on association test statistics deviated from score tests. We demonstrate GhostKnockoffs' performance using empirical simulation and a meta-analysis of nine European ancestral genome-wide association studies and whole exome/genome sequencing studies. Both results demonstrate that GhostKnockoffs identify more putative causal variants with weak genotype-phenotype associations that are missed by conventional GWASs.

Published
2023

2. Rare genetic variation in fibronectin 1 (FN1) protects against APOEε4 in Alzheimer’s disease

Author

Bhattarai, Prabesh, Gunasekaran, Tamil Iniyan, Belloy, Michael E., Reyes-Dumeyer, Dolly, Jülich, Dörthe, Tayran, Hüseyin, Yilmaz, Elanur, Flaherty, Delaney, Turgutalp, Bengisu, Sukumar, Gauthaman, Alba, Camille, McGrath, Elisa Martinez, Hupalo, Daniel N., Bacikova, Dagmar, Le Guen, Yann, Lantigua, Rafael, Medrano, Martin, Rivera, Diones, Recio, Patricia, Nuriel, Tal, Ertekin-Taner, Nilüfer, Teich, Andrew F., Dickson, Dennis W., Holley, Scott, Greicius, Michael, Dalgard, Clifton L., Zody, Michael, Mayeux, Richard, Kizil, Caghan, and Vardarajan, Badri N.

Published
2024
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9. 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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10. Role of the X Chromosome in Alzheimer Disease Genetics.

Author

Belloy, Michael E., Le Guen, Yann, Stewart, Ilaria, Williams, Kennedy, Herz, Joachim, Sherva, Richard, Zhang, Rui, Merritt, Victoria, Panizzon, Matthew S., Hauger, Richard L., Gaziano, J. Michael, Logue, Mark, Napolioni, Valerio, and Greicius, Michael D.

Published
2024
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11. Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.

Author

Kloske, Courtney M., Belloy, Michael E., Blue, Elizabeth E., Bowman, Gregory R., Carrillo, Maria C., Chen, Xiaoying, Chiba‐Falek, Ornit, Davis, Albert A., Paolo, Gilbert Di, Garretti, Francesca, Gate, David, Golden, Lesley R., Heinecke, Jay W., Herz, Joachim, Huang, Yadong, Iadecola, Costantino, Johnson, Lance A., Kanekiyo, Takahisa, Karch, Celeste M., and Khvorova, Anastasia

Published
2024
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12. Beyond guilty by association at scale: searching for causal variants on the basis of genome-wide summary statistics

Author

He, Zihuai, primary, Chu, Benjamin, additional, Yang, James, additional, Gu, Jiaqi, additional, Chen, Zhaomeng, additional, Liu, Linxi, additional, Morrison, Tim, additional, Belloy, Michael E., additional, Qi, Xinran, additional, Hejazi, Nima, additional, Mathur, Maya, additional, Le Guen, Yann, additional, Tang, Hua, additional, Hastie, Trevor, additional, Ionita-laza, Iuliana, additional, Sabatti, Chiara, additional, and Candès, Emmanuel, additional

Published
2024
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13. Long-term ovarian hormone deprivation alters functional connectivity, brain neurochemical profile and white matter integrity in the Tg2576 amyloid mouse model of Alzheimer's disease

Author

Kara, Firat, Belloy, Michael E., Voncken, Rick, Sarwari, Zahra, Garima, Yadav, Anckaerts, Cynthia, Langbeen, An, Leysen, Valerie, Shah, Disha, Jacobs, Jules, Hamaide, Julie, Bols, Peter, Van Audekerke, Johan, Daans, Jasmijn, Guglielmetti, Caroline, Kantarci, Kejal, Prevot, Vincent, Roßner, Steffen, Ponsaerts, Peter, Van der Linden, Annemie, and Verhoye, Marleen

Published
2021
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15. Post‐translational modifications linked to preclinical Alzheimer's disease–related pathological and cognitive changes

Author

Abiose, Olamide, primary, Rutledge, Jarod, additional, Moran‐Losada, Patricia, additional, Belloy, Michael E., additional, Wilson, Edward N., additional, He, Zihuai, additional, Trelle, Alexandra N., additional, Channappa, Divya, additional, Romero, America, additional, Park, Jennifer, additional, Yutsis, Maya V., additional, Sha, Sharon J., additional, Andreasson, Katrin I., additional, Poston, Kathleen L., additional, Henderson, Victor W., additional, Wagner, Anthony D., additional, Wyss‐Coray, Tony, additional, and Mormino, Elizabeth C., additional

Published
2023
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20. APOE loss‐of‐function variants: Compatible with longevity and associated with resistance to Alzheimer’s Disease pathology

Author

Guen, Yann Le, primary, Chemparathy, Augustine, additional, Chen, Sunny, additional, Leong, Lesley, additional, Gorzynski, John John, additional, Xue, Guangxue, additional, Belloy, Michael E, additional, Kasireddy, Nandita, additional, Tauber, Andres Peña, additional, Williams, Kennedy, additional, Wingo, Thomas S., additional, Lah, James J., additional, Jayadev, Suman, additional, Hales, Chadwick M, additional, Peskind, Elaine R, additional, Child, Daniel D, additional, Keene, C Dirk, additional, Le, Cong, additional, Ashley, Euan, additional, Yu, Chang‐En, additional, and Greicius, Michael D, additional

Published
2023
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21. Post‐translational modifications linked to preclinical Alzheimer's disease–related pathological and cognitive changes.

Author

Abiose, Olamide, Rutledge, Jarod, Moran‐Losada, Patricia, Belloy, Michael E., Wilson, Edward N., He, Zihuai, Trelle, Alexandra N., Channappa, Divya, Romero, America, Park, Jennifer, Yutsis, Maya V., Sha, Sharon J., Andreasson, Katrin I., Poston, Kathleen L., Henderson, Victor W., Wagner, Anthony D., Wyss‐Coray, Tony, and Mormino, Elizabeth C.

Abstract

INTRODUCTION: In this study, we leverage proteomic techniques to identify communities of proteins underlying Alzheimer's disease (AD) risk among clinically unimpaired (CU) older adults. METHODS: We constructed a protein co‐expression network using 3869 cerebrospinal fluid (CSF) proteins quantified by SomaLogic, Inc., in a cohort of participants along the AD clinical spectrum. We then replicated this network in an independent cohort of CU older adults and related these modules to clinically‐relevant outcomes. RESULTS: We discovered modules enriched for phosphorylation and ubiquitination that were associated with abnormal amyloid status, as well as p‐tau181 (M4: β = 2.44, p < 0.001, M7: β = 2.57, p < 0.001) and executive function performance (M4: β = −2.00, p = 0.005, M7: β = −2.39, p < 0.001). DISCUSSION: In leveraging CSF proteomic data from individuals spanning the clinical spectrum of AD, we highlight the importance of post‐translational modifications for early cognitive and pathological changes. [ABSTRACT FROM AUTHOR]

Published
2024
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23. APOE loss-of-function variants: Compatible with longevity and associated with resistance to Alzheimer’s disease pathology

Author

Chemparathy, Augustine, Le Guen, Yann, Chen, Sunny, Lee, Eun-Gyung, Leong, Lesley, Gorzynski, John E., Jensen, Tanner D., Ferrasse, Alexis, Xu, Guangxue, Xiang, Hong, Belloy, Michael E., Kasireddy, Nandita, Peña-Tauber, Andrés, Williams, Kennedy, Stewart, Ilaria, Talozzi, Lia, Wingo, Thomas S., Lah, James J., Jayadev, Suman, Hales, Chadwick M., Peskind, Elaine, Child, Daniel D., Roeber, Sigrun, Keene, C. Dirk, Cong, Le, Ashley, Euan A., Yu, Chang-En, and Greicius, Michael D.

Published
2024
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24. Sex‐ and APOE‐specific genetic risk factors for late‐onset Alzheimer's disease: Evidence from gene–gene interaction of longevity‐related loci

Author

Dato, Serena, primary, De Rango, Francesco, additional, Crocco, Paolina, additional, Pallotti, Stefano, additional, Belloy, Michael E., additional, Le Guen, Yann, additional, Greicius, Michael D., additional, Passarino, Giuseppe, additional, Rose, Giuseppina, additional, and Napolioni, Valerio, additional

Published
2023
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25. A 3’UTR Insertion Is a Candidate Causal Variant at theTMEM106BLocus Associated with Increased Risk for FTLD-TDP

Author

Chemparathy, Augustine, primary, Le Guen, Yann, additional, Zeng, Yi, additional, Gorzynski, John, additional, Jensen, Tanner, additional, Yang, Chengran, additional, Kasireddy, Nandita, additional, Talozzi, Lia, additional, Belloy, Michael E., additional, Stewart, Ilaria, additional, Gitler, Aaron D., additional, Wagner, Anthony D., additional, Mormino, Elizabeth, additional, Henderson, Victor W., additional, Wyss-Coray, Tony, additional, Ashley, Euan, additional, Cruchaga, Carlos, additional, and Greicius, Michael D., additional

Published
2023
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26. Charting the genetic architecture of Alzheimer's disease across APOE*4 and sex.

Author

Belloy, Michael E, García‐González, Pablo, Castillo, Atahualpa, Guen, Yann Le, Kasireddy, Nandita, Stewart, Ilaria, Eger, Sarah J, Young, Christina B., Mormino, Elizabeth C., Napolioni, Valerio, He, Zihuai, Altmann, Andre, and Greicius, Michael D

Abstract

Background: APOE*4 status and sex (and their interaction) are among the strongest risk factors for late‐onset Alzheimer's disease (AD). We thus sought to perform large‐scale, stratified genome‐wide association study (GWAS) of AD to chart the role of common genetic variation in AD sexual dimorphism and heterogeneity of APOE*4‐related AD risk. Method: The study overview and GWAS models are shown in Figure.1A. SNP‐array AD GWAS datasets primarily composing the ADGC, together with whole‐genome sequencing (WGS) from ADSP (NG00067.v7), provided case‐control diagnoses for phase‐1. The UK Biobank provided subjects with ICD codes and family history of AD status for phase‐2. Subjects were of European ancestry. Linear mixed model regressions were performed (LMM‐BOLT v.2.3.4) on AD outcome measures, adjusting for sex, APOE*4/APOE*2 dosage, genetic principal components, and array/batch/center. GWAS hits (P<5e‐*8) were evaluated for interactions effects (meta‐regression for phase1+2 meta‐analyses) and assessed in functional follow‐up analyses. The effect of stratification on genetic risk scores (GRS) predictive performance on AD risk was also evaluated. Result: Stratified AD GWAS identified 28 loci/variants, including 5 known lead variants in known AD loci, 6 novel independent variants in known AD loci, and 17 novel loci (Figure.1B). 13 out of 17 novel loci showed varying degrees of functional support, with 4 also showing evidence for QTL colocalization (Figure.2). Many implicated genes showed prior support or effects relevant to AD: MARCHF10 was recently implicated as a risk gene for all‐cause dementia; EMP2 is a regulator of cell membrane composition, cell‐matrix adhesion, and blood vessel endothelial cell migration; SLIT2 binds APP, and EYA4 and TBC1D9 have respectively been implicated in brain tau deposition and MAPT haplotype‐stratified GWAS. Nonetheless, most novel hits were low/uncommon frequency variants and QTL colocalization evidence was limited. Further, there appeared to be no predictive benefit for stratified GRS analyses (Figure.3). Conclusion: We identified novel loci/variants differentially associated with AD risk across APOE*4 and/or sex. Yet, we inferred relatively limited evidence for stratified effects (propensity for low frequency hits and no benefit for stratified GRS). Overall, our findings contribute to our understanding of the genetic etiology of AD, which in turn contributes to advance personalized genetic medicine. [ABSTRACT FROM AUTHOR]

Published
2023
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28. Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Author

Le Guen, Yann, Luo, Guo, Ambati, Aditya, Damotte, Vincent, Jansen, Iris, Yu, Eric, Nicolas, Aude, de Rojasj, Itziar, Leal, Thiago Peixoto, Miyashita, Akinori, Bellenguez, Celine, Lian, Michelle Mulan, Parveen, Kayenat, Morizono, Takashi, Park, Hyeonseul, Grenier-Boley, Benjamin, Naito, Tatsuhiko, Kucukali, Fahri, Talyansky, Seth D., Yogeshwar, Selina Maria, Sempere, Vicente, Satake, Wataru, Alvarez, Victoria, Arosio, Beatrice, Belloy, Michael E., Benussi, Luisa, Boland, Anne, Borroni, Barbara, Bullido, Maria J., Caffarra, Paolo, Clarimon, Jordi, Daniele, Antonio, Darling, Daniel, Debette, Stephanie, Deleuze, Jean-Francois, Dichgans, Martin, Dufouil, Carole, During, Emmanuel, Duzel, Emrah, Galimberti, Daniela, Garcia-Ribas, Guillermo, Maria Garcia-Alberca, Jose, Garcia-Gonzalez, Pablo, Giedraitis, Vilmantas, Goldhardt, Oliver, Graff, Caroline, Grunblatt, Edna, Hanon, Olivier, Hausner, Lucrezia, Heilmann-Heimbach, Stefanie, Holstege, Henne, Hort, Jakub, Jung, Yoo Jin, Jurgen, Deckert, Kern, Silke, Kuulasmaa, Teemu, Lee, Kun Ho, Lin, Ling, Masullo, Carlo, Mecocci, Patrizia, Mehrabian, Shima, de Mendonca, Alexandre, Boada, Merce, Mir, Pablo, Moebus, Susanne, Moreno, Fermin, Nacmias, Benedetta, Nicolas, Gael, Niida, Shumpei, Nordestgaard, Borge G., Papenberg, Goran, Papma, Janne, Parnetti, Lucilla, Pasquier, Florence, Pastor, Pau, Peters, Oliver, Pijnenburg, Yolande A. L., Pinol-Ripoll, Gerard, Popp, Julius, Porcel, Laura Molina, Jordi Perez-Tur, Raquel Puertaj, Rainero, Innocenzo, Ramakers, Inez, Real, Luis M., Riedel-Heller, Steffi, Rodriguez-Rodriguez, Eloy, Ross, Owen A., Royo, Jose Luis, Rujescu, Dan, Scarmeas, Nikolaos, Scheltens, Philip, Scherbaum, Norbert, Schneider, Anja, Seripa, Davide, Skoog, Ingmar, Solfrizzi, Vincenzo, Spalletta, Gianfranco, Squassina, Alessio, van Swieten, John, Sanchez-Valle, Raquel, Tan, Eng-King, Tegos, Thomas, Teunissen, Charlotte, Thomassen, Jesper Qvist, Tremolizzo, Lucio, Vyhnalek, Martin, Verhey, Frans, Waern, Margda, Wiltfang, Jens, Zhangc, Jing, Zetterberg, Henrik, Blennow, Kaj, He, Zihuai, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick G., Andreassen, Ole A., Van Duin, Cornelia, Tsolaki, Magda, Sanchez-Juan, Pascual, Frikke-Schmidt, Ruth, Sleegers, Kristel, Todau, Tatsushi, Zettergren, Anna, Ingelsson, Martin, Okada, Yukinori, Rossi, Giacomina, Hiltunen, Mikko, Gim, Jungsoo, Ozaki, Kouichi, Sims, Rebecca, Foo, Jia Nee, van der Fliere, Wiesje, Ikeuchi, Takeshi, Ramirez, Alfredo, Mata, Ignacio, Ruiz, Agustin, Gan-Or, Ziv, Lambert, Jean-Charles, Greicius, Michael D., Mignot, Emmanuel, Le Guen, Yann, Luo, Guo, Ambati, Aditya, Damotte, Vincent, Jansen, Iris, Yu, Eric, Nicolas, Aude, de Rojasj, Itziar, Leal, Thiago Peixoto, Miyashita, Akinori, Bellenguez, Celine, Lian, Michelle Mulan, Parveen, Kayenat, Morizono, Takashi, Park, Hyeonseul, Grenier-Boley, Benjamin, Naito, Tatsuhiko, Kucukali, Fahri, Talyansky, Seth D., Yogeshwar, Selina Maria, Sempere, Vicente, Satake, Wataru, Alvarez, Victoria, Arosio, Beatrice, Belloy, Michael E., Benussi, Luisa, Boland, Anne, Borroni, Barbara, Bullido, Maria J., Caffarra, Paolo, Clarimon, Jordi, Daniele, Antonio, Darling, Daniel, Debette, Stephanie, Deleuze, Jean-Francois, Dichgans, Martin, Dufouil, Carole, During, Emmanuel, Duzel, Emrah, Galimberti, Daniela, Garcia-Ribas, Guillermo, Maria Garcia-Alberca, Jose, Garcia-Gonzalez, Pablo, Giedraitis, Vilmantas, Goldhardt, Oliver, Graff, Caroline, Grunblatt, Edna, Hanon, Olivier, Hausner, Lucrezia, Heilmann-Heimbach, Stefanie, Holstege, Henne, Hort, Jakub, Jung, Yoo Jin, Jurgen, Deckert, Kern, Silke, Kuulasmaa, Teemu, Lee, Kun Ho, Lin, Ling, Masullo, Carlo, Mecocci, Patrizia, Mehrabian, Shima, de Mendonca, Alexandre, Boada, Merce, Mir, Pablo, Moebus, Susanne, Moreno, Fermin, Nacmias, Benedetta, Nicolas, Gael, Niida, Shumpei, Nordestgaard, Borge G., Papenberg, Goran, Papma, Janne, Parnetti, Lucilla, Pasquier, Florence, Pastor, Pau, Peters, Oliver, Pijnenburg, Yolande A. L., Pinol-Ripoll, Gerard, Popp, Julius, Porcel, Laura Molina, Jordi Perez-Tur, Raquel Puertaj, Rainero, Innocenzo, Ramakers, Inez, Real, Luis M., Riedel-Heller, Steffi, Rodriguez-Rodriguez, Eloy, Ross, Owen A., Royo, Jose Luis, Rujescu, Dan, Scarmeas, Nikolaos, Scheltens, Philip, Scherbaum, Norbert, Schneider, Anja, Seripa, Davide, Skoog, Ingmar, Solfrizzi, Vincenzo, Spalletta, Gianfranco, Squassina, Alessio, van Swieten, John, Sanchez-Valle, Raquel, Tan, Eng-King, Tegos, Thomas, Teunissen, Charlotte, Thomassen, Jesper Qvist, Tremolizzo, Lucio, Vyhnalek, Martin, Verhey, Frans, Waern, Margda, Wiltfang, Jens, Zhangc, Jing, Zetterberg, Henrik, Blennow, Kaj, He, Zihuai, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick G., Andreassen, Ole A., Van Duin, Cornelia, Tsolaki, Magda, Sanchez-Juan, Pascual, Frikke-Schmidt, Ruth, Sleegers, Kristel, Todau, Tatsushi, Zettergren, Anna, Ingelsson, Martin, Okada, Yukinori, Rossi, Giacomina, Hiltunen, Mikko, Gim, Jungsoo, Ozaki, Kouichi, Sims, Rebecca, Foo, Jia Nee, van der Fliere, Wiesje, Ikeuchi, Takeshi, Ramirez, Alfredo, Mata, Ignacio, Ruiz, Agustin, Gan-Or, Ziv, Lambert, Jean-Charles, Greicius, Michael D., and Mignot, Emmanuel

Abstract

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1* 04:07, and intermediary with HLA-DRB1* 04:01 and HLA- DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased A beta 42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.

Published
2023
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29. Association of African Ancestry–Specific APOE Missense Variant R145C With Risk of Alzheimer Disease

Author

Le Guen, Yann, primary, Raulin, Ana-Caroline, additional, Logue, Mark W., additional, Sherva, Richard, additional, Belloy, Michael E., additional, Eger, Sarah J., additional, Chen, Annabel, additional, Kennedy, Gabriel, additional, Kuchenbecker, Lindsey, additional, O’Leary, Justin P., additional, Zhang, Rui, additional, Merritt, Victoria C., additional, Panizzon, Matthew S., additional, Hauger, Richard L., additional, Gaziano, J. Michael, additional, Bu, Guojun, additional, Thornton, Timothy A., additional, Farrer, Lindsay A., additional, Napolioni, Valerio, additional, He, Zihuai, additional, and Greicius, Michael D., additional

Published
2023
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30. Protective association of HLA‐DRB1*04 subtypes in neurodegenerative diseases implicates acetylated tau PHF6 sequences

Author

Guen, Yann Le, primary, Luo, Guo, additional, Ambati, Aditya, additional, Damotte, Vincent, additional, Jansen, Iris E, additional, Yu, Eric, additional, Nicolas, Aude, additional, de Rojas, Itziar, additional, Leal, Thiago Peixoto, additional, Miyashita, Akinori, additional, Bellenguez, Céline, additional, Lian, Michelle Mulan, additional, Parveen, Kayenat, additional, Morizono, Takashi, additional, Park, Hyeonseul, additional, Grenier‐Boley, Benjamin, additional, Naito, Tatsuhiko, additional, Küçükali, Fahri, additional, Talyansky, Seth D., additional, Yogeshwar, Selina Marie, additional, Sempere, Vicente, additional, Satake, Wataru, additional, Álvarez‐Martínez, Victoria, additional, Arosio, Beatrice, additional, Belloy, Michael E, additional, Benussi, Luisa, additional, Boland, Anne, additional, Borroni, Barbara, additional, Bullido, María J., additional, Caffarra, Paolo, additional, Clarimon, Jordi, additional, Daniele, Antonio, additional, Darling, Daniel, additional, Debette, Stéphanie, additional, Deleuze, Jean‐François, additional, Dichgans, Martin, additional, Dufouil, Carole, additional, During, Emmanuel, additional, Duzel, Emrah, additional, Galimberti, Daniela, additional, García‐Ribas, Guillermo, additional, García‐Alberca, Jose María, additional, García‐González, Pablo, additional, Giedraitis, Vilmantas, additional, Goldhardt, Oliver, additional, Graff, Caroline, additional, Grunblatt, Edna, additional, Hanon, Olivier, additional, Hausner, Lucrezia, additional, Heilmann‐Heimbach, Stefanie, additional, Holstege, Henne, additional, Hort, Jakub, additional, Jung, Yoo Jin, additional, Jurgen, Deckert, additional, Kern, Silke, additional, Kuulasmaa, Teemu, additional, Lee, Kun Ho, additional, Ling, Ling, additional, Masullo, Carlo, additional, Mecocci, Patrizia, additional, Mehrabian, Shima, additional, de Mendonça, Alexandre, additional, Boada, Mercè, additional, Mir, Pablo, additional, Moebus, Susanne, additional, Moreno, Fermin, additional, Nacmias, Benedetta, additional, Nicolas, Gaël, additional, Niida, Shumpei, additional, Nordestgaard, Børge G., additional, Papenberg, Goran, additional, Papma, Janne M., additional, Parnetti, Lucilla, additional, Pasquier, Florence, additional, Pastor, Pau, additional, Peters, Oliver, additional, Pijnenburg, Yolande A.L., additional, Piñol‐Ripoll, Gerard, additional, Popp, Julius, additional, Molina, Laura, additional, Puerta, Raquel, additional, Pérez‐Tur, Jordi, additional, Rainero, Innocenzo, additional, Real, Luis Miguel, additional, Riedel‐Heller, Steffi G., additional, Rodríguez, Eloy Rodríguez, additional, Royo, José Luís, additional, Rujescu, Dan, additional, Scarmeas, Nikolaos, additional, Scheltens, Philip, additional, Scherbaum, Norbert, additional, Schneider, Anja, additional, Seripa, Davide, additional, Skoog, Ingmar, additional, Solfrizzi, Vincenzo, additional, Spalletta, Gianfranco, additional, Squassina, Alessio, additional, van Swieten, John C, additional, Sanchez‐Valle, Raquel, additional, Tan, Eng‐King, additional, Tegos, Thomas, additional, Teunissen, Charlotte E., additional, Thomassen, Jesper Qvist, additional, Tremolizzo, Lucio, additional, Vyhnalek, Martin, additional, Verhey, Frans R.J., additional, Waern, Margda, additional, Wiltfang, Jens, additional, Zhang, Jing, additional, Zetterberg, Henrik, additional, Blennow, Kaj, additional, Williams, Julie, additional, Amouyel, Philippe, additional, Jessen, Frank, additional, Kehoe, Patrick G, additional, Andreassen, Ole, additional, van Duijn, Cornelia M, additional, Tsolaki, Magda, additional, Sanchez‐Juan, Pascual, additional, Frikke‐Schmidt, Ruth, additional, Sleegers, Kristel, additional, Toda, Tatsushi, additional, Zettergren, Anna, additional, Ingelsson, Martin, additional, Okada, Yukinori, additional, Rossi, Giacomina, additional, Hiltunen, Mikko, additional, Gim, Jungsoo, additional, Ozaki, Kouichi, additional, Sims, Rebecca, additional, Foo, Jia Nee, additional, van der Flier, Wiesje M., additional, Ikeuchi, Takeshi, additional, Ramirez, Alfredo, additional, Mata, Ignacio, additional, Ruiz, Agustin, additional, Gan‐Or, Ziv, additional, Lambert, Jean‐Charles, additional, Greicius, Michael D, additional, and Mignot, Emmanuel, additional

Published
2022
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33. Rare missense variant (R251G) on APOE counterbalances the Alzheimer’s disease risk associated with APOE‐ε4

Author

Guen, Yann Le, primary, Belloy, Michael E, additional, Grenier‐Boley, Benjamin, additional, de Rojas, Itziar, additional, Castillo, Atahualpa, additional, Jansen, Iris E, additional, Nicolas, Aude, additional, Bellenguez, Céline, additional, Dalmasso, Carolina, additional, Küçükali, Fahri, additional, Eger, Sarah J, additional, Álvarez‐Martínez, Victoria, additional, Arosio, Beatrice, additional, Benussi, Luisa, additional, Boland, Anne, additional, Borroni, Barbara, additional, Bullido, María J., additional, Caffarra, Paolo, additional, Clarimón, Jordi, additional, Daian, Delphine, additional, Daniele, Antonio, additional, Debette, Stéphanie, additional, Deleuze, Jean‐François, additional, Dichgans, Martin, additional, Dufouil, Carole, additional, Duzel, Emrah, additional, Galimberti, Daniela, additional, García‐Alberca, Jose María, additional, García‐González, Pablo, additional, Giedraitis, Vilmantas, additional, Grimmer, Timo, additional, Graff, Caroline, additional, Grunblatt, Edna, additional, Hanon, Olivier, additional, Hausner, Lucrezia, additional, Heilmann‐Heimbach, Stefanie, additional, Holstege, Henne, additional, Hort, Jakub, additional, Jurgen, Deckert, additional, Kuulasmaa, Teemu, additional, van der Lugt, Aad, additional, Masullo, Carlo, additional, Mecocci, Patrizia, additional, Mehrabian, Shima, additional, de Mendonça, Alexandre, additional, Boada, Mercè, additional, Mir, Pablo, additional, Moebus, Susanne, additional, Moreno, Fermin, additional, Nacmias, Benedetta, additional, Nicolas, Gaël, additional, Papenberg, Goran, additional, Parnetti, Lucilla, additional, Pasquier, Florence, additional, Pastor, Pau, additional, Peters, Oliver, additional, Pijnenburg, Yolande A.L., additional, Piñol‐Ripoll, Gerard, additional, Popp, Julius, additional, Molina, Laura, additional, Puerta, Raquel, additional, Pérez‐Tur, Jordi, additional, Rainero, Innocenzo, additional, Ramakers, Inez H.G.B., additional, Rasmussen, Katrine Laura, additional, Real, Luis Miguel, additional, Riedel‐Heller, Steffi G., additional, Rodríguez, Eloy Rodríguez, additional, Royo, José Luís, additional, Rujescu, Dan, additional, Scarmeas, Nikolaos, additional, Scheltens, Philip, additional, Scherbaum, Norbert, additional, Schneider, Anja, additional, Seripa, Davide, additional, Soininen, Hilkka, additional, Solfrizzi, Vincenzo, additional, Spalletta, Gianfranco, additional, Squassina, Alessio, additional, van Swieten, John C, additional, Sanchez‐Valle, Raquel, additional, Tegos, Thomas, additional, Thomassen, Jesper Qvist, additional, Tremolizzo, Lucio, additional, Verhey, Frans R.J., additional, Vyhnalek, Martin, additional, Wiltfang, Jens, additional, He, Zihuai, additional, Napolioni, Valerio, additional, Amouyel, Philippe, additional, Jessen, Frank, additional, Kehoe, Patrick G, additional, van Duijn, Cornelia M, additional, Tsolaki, Magda, additional, Sanchez‐Juan, Pascual, additional, Sleegers, Kristel, additional, Ingelsson, Martin, additional, Rossi, Giacomina, additional, Hiltunen, Mikko, additional, Sims, Rebecca, additional, van der Flier, Wiesje M., additional, Ramirez, Alfredo, additional, Andreassen, Ole, additional, Frikke‐Schmidt, Ruth, additional, Williams, Julie, additional, Ruiz, Agustin, additional, Lambert, Jean‐Charles, additional, and Greicius, Michael D, additional

Published
2022
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35. Additional file 1 of APOE effects on regional tau in preclinical Alzheimer’s disease

Author

Young, Christina B., Johns, Emily, Kennedy, Gabriel, Belloy, Michael E., Insel, Philip S., Greicius, Michael D., Sperling, Reisa A., Johnson, Keith A., Poston, Kathleen L., and Mormino, Elizabeth C.

Abstract

Additional file 1: Supplementary Methods. Description of how amyloid SUVRs are converted to centiloids. Table S1. Demographic information for the 392 Aβ+ CU individuals with tau PET imaging from A4/LEARN. Table S2. Association between amyloid burden (centiloids) and regional tau SUVRs in (A) Aβ- and Aβ+ participants and in (B) only Aβ+ participants from A4/LEARN. Unstandardized beta values (SE), p-values, and model R2 values are listed. Each column represents a separate regression model. Table S3.APOE associations with regional tau SUVRs in 392 Aβ+s with APOE*Age and APOE*Sex interactions included in the model. Unstandardized beta values (SE) and p-values are listed. Each column represents a separate regression model. Table S4. (A) APOE associations with regional tau SUVRs in 359 Aβ+ individuals (B) with APOE*age and APOE*sex interactions after excluding APOE homozygotes (1 e2/e2 participant and 25 e4/e4 participants). Unstandardized beta values (SE) and p-values are listed. Each column represents a separate regression model. Table S5. (A) APOE associations with regional tau SUVRs in 372 Aβ+ individuals (B) with APOE*age and APOE*sex interactions after excluding 13 e2/e4 participants. Unstandardized beta values (SE) and p-values are listed. Each column represents a separate regression model. Table S6. Comparisons of regional tau SUVRs between APOE (A) e2/e3 and e3/e3 groups as well as (B) e3/e4 and e3/e3 groups after adjusting for age and sex. Unstandardized beta values (SE) and p-values are listed. Each column represents a separate regression model. Figure S1. Conversion of global SUVRs to centiloids (CL). (A) Conversion of florbetapir (FBP) global amyloid SUVRs to CLs for A4/LEARN data. (B) Conversion of FBP and florbetaben (FBB) global amyloid SUVRs to CLs for ADNI data. (C) CL distributions across A4/LEARN FBP, ADNI FBP, and ADNI FBB data. Figure S2. Mediation models examining direct and indirect effects of APOE on regional tau SUVRs with continuous amyloid (centiloids) as a mediator in (A) Aβ+ clinically unimpaired (CU) individuals from A4 and (B) Aβ+ CU and mild cognitive impairment (MCI) individuals from ADNI. Both e4 and e2 effects were examined in A4, but only e4 effects were examined in ADNI due to the small sample size of e2 Aβ+ participants in ADNI (n = 13). Unstandardized betas are listed. Note: * p < 0.05, ** p < 0.01, *** p < 0.001. Figure S3. Mediation models examining the effects of APOE4 on regional tau SUVRs with continuous amyloid (centiloids) as a mediator among 162 Aβ+ CU and mild cognitive impairment (MCI) participants who had tau and amyloid PET scans within 2 years of each other. Results are consistent with the effects in the larger ADNI sample. Note: * p < 0.05, ** p < 0.01, *** p < 0.001.

Published
2023
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36. No added value of Sex and APOE*4 stratification for Alzheimer's Disease Genetic Risk Scores.

Author

Belloy, Michael E, Guen, Yann Le, Greicius, Michael D, and Altmann, Andre

Abstract

Background: Genetic risk scores (GRS), be it polygenic risk scores (PRS) or polygenic hazard scores (PHS), have shown promise to support genetic risk prediction and clinical trial recruitment for Alzheimer's disease (AD). A recent study further suggested that sex‐matched AD PHS (e.g., male‐to‐male) outperform sex‐mismatched PHS (e.g., male‐to‐female), while no benefit was observed for PRS. Similar benefits may be expected for matching by APOE*4 positivity status, but this question has remained unexplored. The prior sex‐stratified work neither evaluated whether full sample GRS (males+females) outperform sex‐matched GRS, nor compared polygenic (including many variants regardless of significance) to oligogenic (including fewer more significant variants) effects. Here, we performed the largest‐to‐date sex‐stratified, and first APOE*4‐stratified, evaluation of AD GRS. Methods: The study design is detailed in Figure‐1: genome‐wide association studies (GWAS) were performed in a Discovery cohort (LMM‐BOLT v.2.3.5) and GRS were constructed and evaluated in an independent Replication cohort (PRSice‐2 & R v3.6). All analyses performed multiple linear regression on an AD‐age score that models resilience to age‐related risk for AD (Figure‐2). Models adjusted for sex, APOE*4/APOE*2 dosage (rendering GRS estimates/effects independent of APOE), the first five genetic principal components (PC‐AiR; GENESIS; R v3.6), and array/sequencing center. GRS were evaluated at different P‐value thresholds to elucidate oligogenic versus polygenic effects, while all GRS with other covariates were combined to evaluate predictive performance in the Replication. Results: Stratified discovery GWAS are shown in Figure‐3. GRS tended to perform best at more stringent P‐value thresholds (i.e., oligogenic) and GRS derived from the full‐sample discovery virtually always outperformed stratified GRS (Figure‐4‐5). Predictive performance was similarly the highest for GRS derived from the full‐sample discovery (Table‐1). Conclusions: Our results were consistent with emerging literature supporting that AD is oligogenic and showed that the performance of sex‐ or APOE*4‐stratificatied GRS was outweighed by using full‐sample derived GRS. While not shown here, we made consistent observations when using a case‐control model (thus equivalent to PRS) without age adjustment. These findings have important implications to guide further efforts at translating AD GRS into clinical practice. aging after age 90. [ABSTRACT FROM AUTHOR]

Published
2023
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37. Association of Rare APOE Missense Variants V236E and R251G with Risk of Alzheimer Disease

Author

Le Guen, Yann, Belloy, Michael E, Eger, Sarah J, Mir, Pablo, Moreno, Fermin, Pastor, Pau, Piñol-Ripoll, Gerard, Molina-Porcel, Laura, Pérez-Tur, Jordi, Rodríguez-Rodríguez, Eloy, Royo, Jose Luís, Sánchez-Valle, Raquel, Dichgans, Martin, Rasmussen, Katrine Laura, Rujescu, Dan, Thomassen, Jesper Qvist, Deleuze, Jean-François, He, Zihuai, Napolioni, Valerio, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick Gavin, van Duijn, Cornelia, Grenier-Boley, Benjamin, Tsolaki, Magda, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Rossi, Giacomina, Hiltunen, Mikko, Sims, Rebecca, van der Flier, Wiesje M, Ramirez, Alfredo, Andreassen, Ole A, de Rojas, Itziar, Frikke-Schmidt, Ruth, Williams, Julie, Ruiz, Agustín, Lambert, Jean-Charles, Greicius, Michael D, Members of the EADB, GR@ACE, DEGESCO, DemGene, GERAD, Groups, EADI, Arosio, Beatrice, Benussi, Luisa, Boland, Anne, Castillo-Morales, Atahualpa, Borroni, Barbara, Caffarra, Paolo, Daian, Delphine, Daniele, Antonio, Debette, Stéphanie, Dufouil, Carole, Düzel, Emrah, Galimberti, Daniela, Giedraitis, Vilmantas, Grimmer, Timo, Jansen, Iris, Graff, Caroline, Grünblatt, Edna, Hanon, Olivier, Hausner, Lucrezia, Heilmann-Heimbach, Stefanie, Holstege, Henne, Hort, Jakub, Jürgen, Deckert, Kuulasmaa, Teemu, van der Lugt, Aad, Nicolas, Aude, Masullo, Carlo, Mecocci, Patrizia, Mehrabian, Shima, de Mendonça, Alexandre, Moebus, Susanne, Nacmias, Benedetta, Nicolas, Gael, Olaso, Robert, Papenberg, Goran, Parnetti, Lucilla, Bellenguez, Céline, Pasquier, Florence, Peters, Oliver, Pijnenburg, Yolande A L, Popp, Julius, Rainero, Innocenzo, Ramakers, Inez, Riedel-Heller, Steffi, Scarmeas, Nikolaos, Scheltens, Philip, Scherbaum, Norbert, Dalmasso, Carolina, Schneider, Anja, Seripa, Davide, Soininen, Hilkka, Solfrizzi, Vincenzo, Spalletta, Gianfranco, Squassina, Alessio, van Swieten, John, Tegos, Thomas J, Tremolizzo, Lucio, Verhey, Frans, Küçükali, Fahri, Vyhnalek, Martin, Wiltfang, Jens, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Real, Luis M, Álvarez, Victoria, Bullido, María J, Clarimon, Jordi, García-Alberca, José María, Neurology, Amsterdam Neuroscience - Neurodegeneration, VU University medical center, APH - Personalized Medicine, APH - Methodology, National Institutes of Health (US), National Institute on Aging (US), European Research Council, Pérez-Tur, Jordi [0000-0002-9111-1712], RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychology 2, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), Le Guen, Y, Belloy, M, Grenier-Boley, B, de Rojas, I, Castillo-Morales, A, Jansen, I, Nicolas, A, Bellenguez, C, Dalmasso, C, Küçükali, F, Eger, S, Rasmussen, K, Thomassen, J, Deleuze, J, He, Z, Napolioni, V, Amouyel, P, Jessen, F, Kehoe, P, van Duijn, C, Tsolaki, M, Sánchez-Juan, P, Sleegers, K, Ingelsson, M, Rossi, G, Hiltunen, M, Sims, R, van der Flier, W, Ramirez, A, Andreassen, O, Frikke-Schmidt, R, Williams, J, Ruiz, A, Lambert, J, Greicius, M, Arosio, B, Benussi, L, Boland, A, Borroni, B, Caffarra, P, Daian, D, Daniele, A, Debette, S, Dufouil, C, Düzel, E, Galimberti, D, Giedraitis, V, Grimmer, T, Graff, C, Grünblatt, E, Hanon, O, Hausner, L, Heilmann-Heimbach, S, Holstege, H, Hort, J, Jürgen, D, Kuulasmaa, T, van der Lugt, A, Masullo, C, Mecocci, P, Mehrabian, S, de Mendonça, A, Moebus, S, Nacmias, B, Nicolas, G, Olaso, R, Papenberg, G, Parnetti, L, Pasquier, F, Peters, O, Pijnenburg, Y, Popp, J, Rainero, I, Ramakers, I, Riedel-Heller, S, Scarmeas, N, Scheltens, P, Scherbaum, N, Schneider, A, Seripa, D, Soininen, H, Solfrizzi, V, Spalletta, G, Squassina, A, van Swieten, J, Tegos, T, Tremolizzo, L, Verhey, F, Vyhnalek, M, Wiltfang, J, Boada, M, García-González, P, Puerta, R, Real, L, Álvarez, V, Bullido, M, Clarimon, J, García-Alberca, J, Mir, P, Moreno, F, Pastor, P, Piñol-Ripoll, G, Molina-Porcel, L, Pérez-Tur, J, Rodríguez-Rodríguez, E, Royo, J, Sánchez-Valle, R, Dichgans, M, Rujescu, D, Epidemiology, Radiology & Nuclear Medicine, Graduate School, Medical Psychology, APH - Quality of Care, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), EADB Group, GR@ACE Groupp, DEGESCO Group, DemGene Group, GERAD Group, EADI Group, Repositório da Universidade de Lisboa, and Pérez-Tur, Jordi

Subjects
Male, Genotype, Apolipoprotein E2, epidemiology [Alzheimer Disease], Apolipoprotein E4, Medizin, genetics [Alzheimer Disease], APOLIPOPROTEIN-E, Apolipoproteins E, Settore BIO/13 - Biologia Applicata, Alzheimer Disease, genetics [Apolipoprotein E2], Humans, BEHAVIORAL DEFICITS, ddc:610, Age of Onset, PROGRESS, Alleles, genetics [Apolipoprotein E4], Alzheimer's disease, genetics, APOE, risk factor, A-BETA, Original Investigation, Settore MED/26 - NEUROLOGIA, ALLELE, genetics [Apolipoproteins E], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, INFERENCE, Neurology (clinical), Human medicine
Abstract

34 páginas, 2 tablas, 2 figuras. 2 ficheros con material suplementario. Data used in preparation of this manuscript can be obtained upon application at: - dbGaP (https://www.ncbi.nlm.nih.gov/gap/advanced_search/) - NIAGADS and NIAGADS DSS (https://www.niagads.org/) - LONI (https://ida.loni.usc.edu/) - Synapse (https://adknowledgeportal.synapse.org/) - RADC Rush (https://www.radc.rush.edu/) - NACC (https://naccdata.org/) - UK Biobank (https://biobank.ndph.ox.ac.uk/showcase/), The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide critical new insights, but given the low frequency of additional missense variants, AD genetic cohorts have previously been too small to interrogate this question robustly., This work was supported by the National Institute of Health and National Institute of Aging grants AG060747 (MDG), AG066206 (ZH), AG066515 (ZH, MDG), the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie (grant agreement No. 890650, YLG), the Alzheimer’s Association (AARF-20-683984, MEB), and the Iqbal Farrukh and Asad Jamal Fund, a grant from the EU Joint Programme – Neurodegenerative Disease Research (European Alzheimer DNA BioBank, EADB; JPND). Inserm UMR1167 is also funded by the Inserm, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine, and the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to Alzheimer’s disease). EADB thank the study participants, researchers, and staff for collecting and contributing to the data, the high-performance computing service at the University of Lille, and the staff at CEA-CNRGH for their help with sample preparation and genotyping, and technical assistance. Additional funders of individual investigators and institutions who contributed to data collection and genotyping are provided in the Supplemental Online Content.

Published
2022

38. Supplemental Online Content. Association of Rare APOE Missense Variants V236E and R251G With Risk of Alzheimer Disease

Author

Le Guen, Yann, Belloy, Michael E, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo-Morales, Atahualpa, Jansen, Iris, Nicolas, Aude, Bellenguez, Céline, Dalmasso, Carolina, Küçükali, Fahri, Eger, Sarah J, Jürgen, Deckert, Kuulasmaa, Teemu, van der Lugt, Aad, Masullo, Carlo, Mecocci, Patrizia, Mehrabian, Shima, de Mendonça, Alexandre, Moebus, Susanne, Nacmias, Benedetta, Nicolas, Gael, Olaso, Robert, Papenberg, Goran, Parnetti, Lucilla, Pasquier, Florence, Peters, Oliver, Pijnenburg, Yolande A L, Popp, Julius, Rainero, Innocenzo, Ramakers, Inez, Riedel-Heller, Steffi, Scarmeas, Nikolaos, Scheltens, Philip, Scherbaum, Norbert, Schneider, Anja, Seripa, Davide, Soininen, Hilkka, Solfrizzi, Vincenzo, Spalletta, Gianfranco, Squassina, Alessio, van Swieten, John, Tegos, Thomas J, Tremolizzo, Lucio, Verhey, Frans, Vyhnalek, Martin, Wiltfang, Jens, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Real, Luis Miguel, Álvarez, Victoria, Bullido, María J., Clarimón, Jordi, García-Alberca, José María, Mir, Pablo, Moreno, Fermín, Pastor, Pau, Piñol-Ripoll, Gerard, Molina-Porcel, Laura, Pérez-Tur, Jordi, Rodríguez Martínez, Eloy, Royo, José Luis, Sánchez-Valle, Raquel, Dichgans, Martin, Rujescu, Dan, Rasmussen, Katrine Laura, Thomassen, Jesper Qvist, Deleuze, Jean-François, He, Zihuai, Napolioni, Valerio, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick G., van Duijn, Cornelia, Tsolaki, Magda, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Rossi, Giacomina, Hiltunen, Mikko, Sims, Rebecca, van der Flier, Wiesje M., Ramírez, Alfredo, Andreassen, Ole A., Frikke-Schmidt, Ruth, Williams, Julie, Ruiz, Agustín, Lambert, Jean-Charles, Greicius, Michael D, Arosio, Beatrice, Benussi, Luisa, Boland, Anne, Borroni, Barbara, Caffarra, Paolo, Daian, Delphine, Daniele, Antonio, Debette, Stéphanie, Dufouil, Carole, Düzel, Emrah, Galimberti, Daniela, Giedraitis, Vilmantas, Grimmer, Timo, Graff, Caroline, Grünblatt, Edna, Hanon, Olivier, Hausner, Lucrezia, Heilmann-Heimbach, Stefanie, Holstege, Henne, Hort, Jakub, Le Guen, Yann, Belloy, Michael E, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo-Morales, Atahualpa, Jansen, Iris, Nicolas, Aude, Bellenguez, Céline, Dalmasso, Carolina, Küçükali, Fahri, Eger, Sarah J, Jürgen, Deckert, Kuulasmaa, Teemu, van der Lugt, Aad, Masullo, Carlo, Mecocci, Patrizia, Mehrabian, Shima, de Mendonça, Alexandre, Moebus, Susanne, Nacmias, Benedetta, Nicolas, Gael, Olaso, Robert, Papenberg, Goran, Parnetti, Lucilla, Pasquier, Florence, Peters, Oliver, Pijnenburg, Yolande A L, Popp, Julius, Rainero, Innocenzo, Ramakers, Inez, Riedel-Heller, Steffi, Scarmeas, Nikolaos, Scheltens, Philip, Scherbaum, Norbert, Schneider, Anja, Seripa, Davide, Soininen, Hilkka, Solfrizzi, Vincenzo, Spalletta, Gianfranco, Squassina, Alessio, van Swieten, John, Tegos, Thomas J, Tremolizzo, Lucio, Verhey, Frans, Vyhnalek, Martin, Wiltfang, Jens, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Real, Luis Miguel, Álvarez, Victoria, Bullido, María J., Clarimón, Jordi, García-Alberca, José María, Mir, Pablo, Moreno, Fermín, Pastor, Pau, Piñol-Ripoll, Gerard, Molina-Porcel, Laura, Pérez-Tur, Jordi, Rodríguez Martínez, Eloy, Royo, José Luis, Sánchez-Valle, Raquel, Dichgans, Martin, Rujescu, Dan, Rasmussen, Katrine Laura, Thomassen, Jesper Qvist, Deleuze, Jean-François, He, Zihuai, Napolioni, Valerio, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick G., van Duijn, Cornelia, Tsolaki, Magda, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Rossi, Giacomina, Hiltunen, Mikko, Sims, Rebecca, van der Flier, Wiesje M., Ramírez, Alfredo, Andreassen, Ole A., Frikke-Schmidt, Ruth, Williams, Julie, Ruiz, Agustín, Lambert, Jean-Charles, Greicius, Michael D, Arosio, Beatrice, Benussi, Luisa, Boland, Anne, Borroni, Barbara, Caffarra, Paolo, Daian, Delphine, Daniele, Antonio, Debette, Stéphanie, Dufouil, Carole, Düzel, Emrah, Galimberti, Daniela, Giedraitis, Vilmantas, Grimmer, Timo, Graff, Caroline, Grünblatt, Edna, Hanon, Olivier, Hausner, Lucrezia, Heilmann-Heimbach, Stefanie, Holstege, Henne, and Hort, Jakub

Abstract

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

Published
2022

39. 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, Greicius, Michael D., 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.

Abstract

BACKGROUND: Genetic variants within the APOE locus may modulate Alzheimer's disease (AD) risk independently or in conjunction with APOE*2/3/4 genotypes. Identifying such variants and mechanisms would importantly advance our understanding of APOE pathophysiology and provide critical guidance for AD therapies aimed at APOE. The APOE locus however remains relatively poorly understood in AD, owing to multiple challenges that include its complex linkage structure and uncertainty in APOE*2/3/4 genotype quality. Here, we present a novel APOE*2/3/4 filtering approach and showcase its relevance on AD risk association analyses for the rs439401 variant, which is located 1801 base pairs downstream of APOE and has been associated with a potential regulatory effect on APOE. METHODS: We used thirty-two AD-related cohorts, with genetic data from various high-density single-nucleotide polymorphism microarrays, whole-genome sequencing, and whole-exome sequencing. Study participants were filtered to be ages 60 and older, non-Hispanic, of European ancestry, and diagnosed as cognitively normal or AD (n = 65,701). Primary analyses investigated AD risk in APOE*4/4 carriers. Additional supporting analyses were performed in APOE*3/4 and 3/3 strata. Outcomes were compared under two different APOE*2/3/4 filtering approaches. RESULTS: Using more conventional APOE*2/3/4 filtering criteria (approach 1), we showed that, when in-phase with APOE*4, rs439401 was variably associated with protective effects on AD case-control status. However, when applying a novel filter that increases the certainty of the APOE*2/3/4 genotypes by applying more stringent criteria for concordance between the provided APOE genotype and imputed APOE genotype (approach 2), we observed that all significant effects were lost. CONCLUSIONS: We showed that careful consideration of APOE genotype and appropriate sample filtering were crucial to robustly interrogate the role of the APOE locus on AD risk. Our study presents a no

Published
2022

40. Additional file 1 of 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, S��nchez-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.

Abstract

Additional file 1. Supplementary material.

Published
2022
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41. Summary statistics knockoff inference empowers identification of putative causal variants in genome-wide association studies

Author

He, Zihuai, primary, Liu, Linxi, additional, Belloy, Michael E., additional, Le Guen, Yann, additional, Sossin, Aaron, additional, Liu, Xiaoxia, additional, Qi, Xinran, additional, Ma, Shiyang, additional, Wyss-Coray, Tony, additional, Tang, Hua, additional, Sabatti, Chiara, additional, Candes, Emmanuel, additional, Greicius, Michael D., additional, and Ionita-Laza, Iuliana, additional

Published
2021
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42. Genome-wide analysis of common and rare variants via multiple knockoffs at biobank scale, with an application to Alzheimer disease genetics

Author

He, Zihuai, primary, Le Guen, Yann, additional, Liu, Linxi, additional, Lee, Justin, additional, Ma, Shiyang, additional, Yang, Andrew C., additional, Liu, Xiaoxia, additional, Rutledge, Jarod, additional, Losada, Patricia Moran, additional, Song, Bowen, additional, Belloy, Michael E., additional, Butler, Robert R., additional, Longo, Frank M., additional, Tang, Hua, additional, Mormino, Elizabeth C., additional, Wyss-Coray, Tony, additional, Greicius, Michael D., additional, and Ionita-Laza, Iuliana, additional

Published
2021
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49. Long‐term deprivation of ovarian hormones via ovariectomy alters functional connectivity, brain neurochemistry and white matter integrity in a mouse model of Alzheimer's disease

Author

Kara, Firat, primary, Belloy, Michael E, additional, Voncken, Rick, additional, Sarwari, Zahra, additional, Yadav, Garima, additional, Anckaerts, Cynthia, additional, Langbeen, An, additional, Leysen, Valérie, additional, Shah, Disha, additional, Jacobs, Jules, additional, Hamaide, Julie, additional, Bols, Peter, additional, Van Audekerke, Johan, additional, Daans, Jasmijn, additional, Guglielmetti, Caroline, additional, Kantarci, Kejal, additional, Prevot, Vincent, additional, Rossner, Steffen, additional, Ponsaerts, Peter, additional, Van Der Linden, Annemie, additional, and Verhoye, Marleen, additional

Published
2020
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