Search

Your search keyword '"Nicolas, Aude"' showing total 7 results
Start Over Author "Nicolas, Aude" Publisher uppsala universitet, geriatrik
7 results on '"Nicolas, Aude"'

1. Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease

Author

Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Kuecuekali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Juergen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Duezel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Perez-Tur, Jordi, Bullido, Maria J., Pastor, Pau, Sanchez-Valle, Raquel, Alvarez, Victoria, Boada, Merce, Garcia-Gonzalez, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Pinol-Ripoll, Gerard, Garcia-Alberca, Jose Maria, Royo, Jose Luis, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, de Mendonca, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Gruenblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sanchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustin, Ramirez, Alfredo, Lambert, Jean-Charles, Frikke-Schmidt, Ruth, Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Kuecuekali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Juergen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Duezel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Perez-Tur, Jordi, Bullido, Maria J., Pastor, Pau, Sanchez-Valle, Raquel, Alvarez, Victoria, Boada, Merce, Garcia-Gonzalez, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Pinol-Ripoll, Gerard, Garcia-Alberca, Jose Maria, Royo, Jose Luis, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, de Mendonca, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Gruenblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sanchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustin, Ramirez, Alfredo, Lambert, Jean-Charles, and Frikke-Schmidt, Ruth

Abstract

IMPORTANCE An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. OBJECTIVE To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Bio

Published
2023
Full Text
View/download PDF

2. Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease

Author

Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Kuecuekali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Juergen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Duezel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Perez-Tur, Jordi, Bullido, Maria J., Pastor, Pau, Sanchez-Valle, Raquel, Alvarez, Victoria, Boada, Merce, Garcia-Gonzalez, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Pinol-Ripoll, Gerard, Garcia-Alberca, Jose Maria, Royo, Jose Luis, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, de Mendonca, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Gruenblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sanchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustin, Ramirez, Alfredo, Lambert, Jean-Charles, Frikke-Schmidt, Ruth, Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Kuecuekali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Juergen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Duezel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Perez-Tur, Jordi, Bullido, Maria J., Pastor, Pau, Sanchez-Valle, Raquel, Alvarez, Victoria, Boada, Merce, Garcia-Gonzalez, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Pinol-Ripoll, Gerard, Garcia-Alberca, Jose Maria, Royo, Jose Luis, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, de Mendonca, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Gruenblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sanchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustin, Ramirez, Alfredo, Lambert, Jean-Charles, and Frikke-Schmidt, Ruth

Abstract

IMPORTANCE An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. OBJECTIVE To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Bio

Published
2023
Full Text
View/download PDF

3. Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease

Author

Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Kuecuekali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Juergen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Duezel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Perez-Tur, Jordi, Bullido, Maria J., Pastor, Pau, Sanchez-Valle, Raquel, Alvarez, Victoria, Boada, Merce, Garcia-Gonzalez, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Pinol-Ripoll, Gerard, Garcia-Alberca, Jose Maria, Royo, Jose Luis, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, de Mendonca, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Gruenblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sanchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustin, Ramirez, Alfredo, Lambert, Jean-Charles, Frikke-Schmidt, Ruth, Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Kuecuekali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Juergen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Duezel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Perez-Tur, Jordi, Bullido, Maria J., Pastor, Pau, Sanchez-Valle, Raquel, Alvarez, Victoria, Boada, Merce, Garcia-Gonzalez, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Pinol-Ripoll, Gerard, Garcia-Alberca, Jose Maria, Royo, Jose Luis, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, de Mendonca, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Gruenblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sanchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustin, Ramirez, Alfredo, Lambert, Jean-Charles, and Frikke-Schmidt, Ruth

Abstract

IMPORTANCE An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. OBJECTIVE To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Bio

Published
2023
Full Text
View/download PDF

4. Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease

Author

Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Kuecuekali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Juergen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Duezel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Perez-Tur, Jordi, Bullido, Maria J., Pastor, Pau, Sanchez-Valle, Raquel, Alvarez, Victoria, Boada, Merce, Garcia-Gonzalez, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Pinol-Ripoll, Gerard, Garcia-Alberca, Jose Maria, Royo, Jose Luis, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, de Mendonca, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Gruenblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sanchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustin, Ramirez, Alfredo, Lambert, Jean-Charles, Frikke-Schmidt, Ruth, Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Kuecuekali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Juergen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Duezel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Perez-Tur, Jordi, Bullido, Maria J., Pastor, Pau, Sanchez-Valle, Raquel, Alvarez, Victoria, Boada, Merce, Garcia-Gonzalez, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Pinol-Ripoll, Gerard, Garcia-Alberca, Jose Maria, Royo, Jose Luis, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, de Mendonca, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Gruenblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sanchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustin, Ramirez, Alfredo, Lambert, Jean-Charles, and Frikke-Schmidt, Ruth

Abstract

IMPORTANCE An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. OBJECTIVE To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Bio

Published
2023
Full Text
View/download PDF

5. Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease

Author

Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Kuecuekali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Juergen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Duezel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Perez-Tur, Jordi, Bullido, Maria J., Pastor, Pau, Sanchez-Valle, Raquel, Alvarez, Victoria, Boada, Merce, Garcia-Gonzalez, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Pinol-Ripoll, Gerard, Garcia-Alberca, Jose Maria, Royo, Jose Luis, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, de Mendonca, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Gruenblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sanchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustin, Ramirez, Alfredo, Lambert, Jean-Charles, Frikke-Schmidt, Ruth, Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Kuecuekali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Juergen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Duezel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Perez-Tur, Jordi, Bullido, Maria J., Pastor, Pau, Sanchez-Valle, Raquel, Alvarez, Victoria, Boada, Merce, Garcia-Gonzalez, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Pinol-Ripoll, Gerard, Garcia-Alberca, Jose Maria, Royo, Jose Luis, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, de Mendonca, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Gruenblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sanchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustin, Ramirez, Alfredo, Lambert, Jean-Charles, and Frikke-Schmidt, Ruth

Abstract

IMPORTANCE An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. OBJECTIVE To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Bio

Published
2023
Full Text
View/download PDF

6. 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, Celine, Dalmasso, Carolina, Kucukali, Fahri, Eger, Sarah J., Rasmussen, Katrine Laura, Thomassen, Jesper Qvist, Deleuze, Jean-Francois, He, Zihuai, Napolioni, Valerio, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick G., van Duijn, Cornelia, Tsolaki, Magda, Sanchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Rossi, Giacomina, Hiltunen, Mikko, Sims, Rebecca, van der Flier, Wiesje M., Ramirez, Alfredo, Andreassen, Ole A., Frikke-Schmidt, Ruth, Williams, Julie, Ruiz, Agustin, Lambert, Jean-Charles, Greicius, Michael D., Le Guen, Yann, Belloy, Michael E., Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo-Morales, Atahualpa, Jansen, Iris, Nicolas, Aude, Bellenguez, Celine, Dalmasso, Carolina, Kucukali, Fahri, Eger, Sarah J., Rasmussen, Katrine Laura, Thomassen, Jesper Qvist, Deleuze, Jean-Francois, He, Zihuai, Napolioni, Valerio, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick G., van Duijn, Cornelia, Tsolaki, Magda, Sanchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Rossi, Giacomina, Hiltunen, Mikko, Sims, Rebecca, van der Flier, Wiesje M., Ramirez, Alfredo, Andreassen, Ole A., Frikke-Schmidt, Ruth, Williams, Julie, Ruiz, Agustin, Lambert, Jean-Charles, and Greicius, Michael D.

Abstract

Importance The APOE epsilon 2 and APOE epsilon 4 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 epsilon 2 and APOE epsilon 4 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. Objective To determine whether rare missense variants on APOE are associated with AD risk. Design, Setting and Participants Association with case-control status was tested in a sequenced discovery sample (stage 1) and followed up in several microarray imputed cohorts as well as the UK Biobank whole-exome sequencing resource using a proxy-AD phenotype (stages 2 and 3). This study combined case-control, family-based, population-based, and longitudinal AD-related cohorts that recruited referred and volunteer participants. Stage 1 induded 37 409 nonunique participants of European or admixed European ancestry, with 11868 individuals with AD and 11 934 controls passing analysis inclusion criteria. In stages 2 and 3, 475 473 participants were considered across 8 cohorts, of which 84513 individuals with AD and proxy-AD and 328 372 controls passed inclusion criteria. Selection criteria were cohort specific, and this study was performed a posteriori on individuals who were genotyped. Among the available genotypes, 76 195 were excluded. All data were retrieved between September 2015 and November 2021 and analyzed between April and November 2021. Main Outcomes ans Measures In primary analyses, the AD risk associated with each missense variant was estimated, as appropriate, with either linear mixed-model regression or logistic regression. In secondary analyses, associations were e

Published
2022
Full Text
View/download PDF

7. Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

Author

Mahajan, Anubha, Spracklen, Cassandra N., Zhang, Weihua, Ng, Maggie C. Y., Petty, Lauren E., Kitajima, Hidetoshi, Yu, Grace Z., Rueger, Sina, Speidel, Leo, Kim, Young Jin, Horikoshi, Momoko, Mercader, Josep M., Taliun, Daniel, Moon, Sanghoon, Kwak, Soo-Heon, Robertson, Neil R., Rayner, Nigel W., Loh, Marie, Kim, Bong-Jo, Chiou, Joshua, Miguel-Escalada, Irene, Parolo, Pietro della Briotta, Lin, Kuang, Bragg, Fiona, Preuss, Michael H., Takeuchi, Fumihiko, Nano, Jana, Guo, Xiuqing, Lamri, Amel, Nakatochi, Masahiro, Scott, Robert A., Lee, Jung-Jin, Huerta-Chagoya, Alicia, Graff, Mariaelisa, Chai, Jin-Fang, Parra, Esteban J., Yao, Jie, Bielak, Lawrence F., Tabara, Yasuharu, Hai, Yang, Steinthorsdottir, Valgerdur, Cook, James P., Kals, Mart, Grarup, Niels, Schmidt, Ellen M., Pan, Ian, Sofer, Tamar, Wuttke, Matthias, Sarnowski, Chloe, Gieger, Christian, Nousome, Darryl, Trompet, Stella, Long, Jirong, Sun, Meng, Tong, Lin, Chen, Wei-Min, Ahmad, Meraj, Noordam, Raymond, Lim, Victor J. Y., Tam, Claudia H. T., Joo, Yoonjung Yoonie, Chen, Chien-Hsiun, Raffield, Laura M., Lecoeur, Cecile, Prins, Bram Peter, Nicolas, Aude, Yanek, Lisa R., Chen, Guanjie, Jensen, Richard A., Tajuddin, Salman, Kabagambe, Edmond K., An, Ping, Xiang, Anny H., Choi, Hyeok Sun, Cade, Brian E., Tan, Jingyi, Flanagan, Jack, Abaitua, Fernando, Adair, Linda S., Adeyemo, Adebowale, Aguilar-Salinas, Carlos A., Akiyama, Masato, Anand, Sonia S., Bertoni, Alain, Bian, Zheng, Bork-Jensen, Jette, Brandslund, Ivan, Brody, Jennifer A., Brummett, Chad M., Buchanan, Thomas A., Canouil, Mickael, Chan, Juliana C. N., Chang, Li-Ching, Chee, Miao-Li, Chen, Ji, Chen, Shyh-Huei, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, Cushman, Mary, Das, Swapan K., de Silva, H. Janaka, Dedoussis, George, Dimitrov, Latchezar, Doumatey, Ayo P., Du, Shufa, Duan, Qing, Eckardt, Kai-Uwe, Emery, Leslie S., Evans, Daniel S., Evans, Michele K., Fischer, Krista, Floyd, James S., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Frayling, Timothy M., Freedman, Barry, I, Fuchsberger, Christian, Genter, Pauline, Gerstein, Hertzel C., Giedraitis, Vilmantas, Gonzalez-Villalpando, Clicerio, Gonzalez-Villalpando, Maria Elena, Goodarzi, Mark O., Gordon-Larsen, Penny, Gorkin, David, Gross, Myron, Guo, Yu, Hackinger, Sophie, Han, Sohee, Hattersley, Andrew T., Herder, Christian, Howard, Annie-Green, Hsueh, Willa, Huang, Mengna, Huang, Wei, Hung, Yi-Jen, Hwang, Mi Yeong, Hwu, Chii-Min, Ichihara, Sahoko, Ikram, Mohammad Arfan, Ingelsson, Martin, Islam, Md Tariqul, Isono, Masato, Jang, Hye-Mi, Jasmine, Farzana, Jiang, Guozhi, Jonas, Jost B., Jorgensen, Marit E., Jorgensen, Torben, Kamatani, Yoichiro, Kandeel, Fouad R., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kaur, Varinderpal, Kawaguchi, Takahisa, Keaton, Jacob M., Kho, Abel N., Khor, Chiea-Chuen, Kibriya, Muhammad G., Kim, Duk-Hwan, Kohara, Katsuhiko, Kriebel, Jennifer, Kronenberg, Florian, Kuusisto, Johanna, Lall, Kristi, Lange, Leslie A., Lee, Myung-Shik, Lee, Nanette R., Leong, Aaron, Li, Liming, Li, Yun, Li-Gao, Ruifang, Ligthart, Symen, Lindgren, Cecilia M., Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Locke, Adam E., Louie, Tin, Luan, Jian'an, Luk, Andrea O., Luo, Xi, Lv, Jun, Lyssenko, Valeriya, Mamakou, Vasiliki, Mani, K. Radha, Meitinger, Thomas, Metspalu, Andres, Morris, Andrew D., Nadkarni, Girish N., Nadler, Jerry L., Nalls, Michael A., Nayak, Uma, Nongmaithem, Suraj S., Ntalla, Ioanna, Okada, Yukinori, Orozco, Lorena, Patel, Sanjay R., Pereira, Mark A., Peters, Annette, Pirie, Fraser J., Porneala, Bianca, Prasad, Gauri, Preissl, Sebastian, Rasmussen-Torvik, Laura J., Reiner, Alexander P., Roden, Michael, Rohde, Rebecca, Roll, Kathryn, Sabanayagam, Charumathi, Sander, Maike, Sandow, Kevin, Sattar, Naveed, Schonherr, Sebastian, Schurmann, Claudia, Shahriar, Mohammad, Shi, Jinxiu, Shin, Dong Mun, Shriner, Daniel, Smith, Jennifer A., So, Wing Yee, Stancakova, Alena, Stilp, Adrienne M., Strauch, Konstantin, Suzuki, Ken, Takahashi, Atsushi, Taylor, Kent D., Thorand, Barbara, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tomlinson, Brian, Torres, Jason M., Tsai, Fuu-Jen, Tuomilehto, Jaakko, Tusie-Luna, Teresa, Udler, Miriam S., Valladares-Salgado, Adan, van Dam, Rob M., van Klinken, Jan B., Varma, Rohit, Vujkovic, Marijana, Wacher-Rodarte, Niels, Wheeler, Eleanor, Whitsel, Eric A., Wickremasinghe, Ananda R., van Dijk, Ko Willems, Witte, Daniel R., Yajnik, Chittaranjan S., Yamamoto, Ken, Yamauchi, Toshimasa, Yengo, Loic, Yoon, Kyungheon, Yu, Canqing, Yuan, Jian-Min, Yusuf, Salim, Zhang, Liang, Zheng, Wei, Raffel, Leslie J., Igase, Michiya, Ipp, Eli, Redline, Susan, Cho, Yoon Shin, Lind, Lars, Province, Michael A., Hanis, Craig L., Peyser, Patricia A., Ingelsson, Erik, Zonderman, Alan B., Psaty, Bruce M., Wang, Ya-Xing, Rotimi, Charles N., Becker, Diane M., Matsuda, Fumihiko, Liu, Yongmei, Zeggini, Eleftheria, Yokota, Mitsuhiro, Rich, Stephen S., Kooperberg, Charles, Pankow, James S., Engert, James C., Chen, Yii-Der Ida, Froguel, Philippe, Wilson, James G., Sheu, Wayne H. H., Kardia, Sharon L. R., Wu, Jer-Yuarn, Hayes, M. Geoffrey, Ma, Ronald C. W., Wong, Tien-Yin, Groop, Leif, Mook-Kanamori, Dennis O., Chandak, Giriraj R., Collins, Francis S., Bharadwaj, Dwaipayan, Pare, Guillaume, Sale, Michele M., Ahsan, Habibul, Motala, Ayesha A., Shu, Xiao-Ou, Park, Kyong-Soo, Jukema, J. Wouter, Cruz, Miguel, McKean-Cowdin, Roberta, Grallert, Harald, Cheng, Ching-Yu, Bottinger, Erwin P., Dehghan, Abbas, Tai, E-Shyong, Dupuis, Josee, Kato, Norihiro, Laakso, Markku, Kottgen, Anna, Koh, Woon-Puay, Palmer, Colin N. A., Liu, Simin, Abecasis, Goncalo, Kooner, Jaspal S., Loos, Ruth J. F., North, Kari E., Haiman, Christopher A., Florez, Jose C., Saleheen, Danish, Hansen, Torben, Pedersen, Oluf, Magi, Reedik, Langenberg, Claudia, Wareham, Nicholas J., Maeda, Shiro, Kadowaki, Takashi, Lee, Juyoung, Millwood, Iona Y., Walters, Robin G., Stefansson, Kari, Myers, Simon R., Ferrer, Jorge, Gaulton, Kyle J., Meigs, James B., Mohlke, Karen L., Gloyn, Anna L., Bowden, Donald W., Below, Jennifer E., Chambers, John C., Sim, Xueling, Boehnke, Michael, Rotter, Jerome, I, McCarthy, Mark, I, Morris, Andrew P., Mahajan, Anubha, Spracklen, Cassandra N., Zhang, Weihua, Ng, Maggie C. Y., Petty, Lauren E., Kitajima, Hidetoshi, Yu, Grace Z., Rueger, Sina, Speidel, Leo, Kim, Young Jin, Horikoshi, Momoko, Mercader, Josep M., Taliun, Daniel, Moon, Sanghoon, Kwak, Soo-Heon, Robertson, Neil R., Rayner, Nigel W., Loh, Marie, Kim, Bong-Jo, Chiou, Joshua, Miguel-Escalada, Irene, Parolo, Pietro della Briotta, Lin, Kuang, Bragg, Fiona, Preuss, Michael H., Takeuchi, Fumihiko, Nano, Jana, Guo, Xiuqing, Lamri, Amel, Nakatochi, Masahiro, Scott, Robert A., Lee, Jung-Jin, Huerta-Chagoya, Alicia, Graff, Mariaelisa, Chai, Jin-Fang, Parra, Esteban J., Yao, Jie, Bielak, Lawrence F., Tabara, Yasuharu, Hai, Yang, Steinthorsdottir, Valgerdur, Cook, James P., Kals, Mart, Grarup, Niels, Schmidt, Ellen M., Pan, Ian, Sofer, Tamar, Wuttke, Matthias, Sarnowski, Chloe, Gieger, Christian, Nousome, Darryl, Trompet, Stella, Long, Jirong, Sun, Meng, Tong, Lin, Chen, Wei-Min, Ahmad, Meraj, Noordam, Raymond, Lim, Victor J. Y., Tam, Claudia H. T., Joo, Yoonjung Yoonie, Chen, Chien-Hsiun, Raffield, Laura M., Lecoeur, Cecile, Prins, Bram Peter, Nicolas, Aude, Yanek, Lisa R., Chen, Guanjie, Jensen, Richard A., Tajuddin, Salman, Kabagambe, Edmond K., An, Ping, Xiang, Anny H., Choi, Hyeok Sun, Cade, Brian E., Tan, Jingyi, Flanagan, Jack, Abaitua, Fernando, Adair, Linda S., Adeyemo, Adebowale, Aguilar-Salinas, Carlos A., Akiyama, Masato, Anand, Sonia S., Bertoni, Alain, Bian, Zheng, Bork-Jensen, Jette, Brandslund, Ivan, Brody, Jennifer A., Brummett, Chad M., Buchanan, Thomas A., Canouil, Mickael, Chan, Juliana C. N., Chang, Li-Ching, Chee, Miao-Li, Chen, Ji, Chen, Shyh-Huei, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, Cushman, Mary, Das, Swapan K., de Silva, H. Janaka, Dedoussis, George, Dimitrov, Latchezar, Doumatey, Ayo P., Du, Shufa, Duan, Qing, Eckardt, Kai-Uwe, Emery, Leslie S., Evans, Daniel S., Evans, Michele K., Fischer, Krista, Floyd, James S., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Frayling, Timothy M., Freedman, Barry, I, Fuchsberger, Christian, Genter, Pauline, Gerstein, Hertzel C., Giedraitis, Vilmantas, Gonzalez-Villalpando, Clicerio, Gonzalez-Villalpando, Maria Elena, Goodarzi, Mark O., Gordon-Larsen, Penny, Gorkin, David, Gross, Myron, Guo, Yu, Hackinger, Sophie, Han, Sohee, Hattersley, Andrew T., Herder, Christian, Howard, Annie-Green, Hsueh, Willa, Huang, Mengna, Huang, Wei, Hung, Yi-Jen, Hwang, Mi Yeong, Hwu, Chii-Min, Ichihara, Sahoko, Ikram, Mohammad Arfan, Ingelsson, Martin, Islam, Md Tariqul, Isono, Masato, Jang, Hye-Mi, Jasmine, Farzana, Jiang, Guozhi, Jonas, Jost B., Jorgensen, Marit E., Jorgensen, Torben, Kamatani, Yoichiro, Kandeel, Fouad R., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kaur, Varinderpal, Kawaguchi, Takahisa, Keaton, Jacob M., Kho, Abel N., Khor, Chiea-Chuen, Kibriya, Muhammad G., Kim, Duk-Hwan, Kohara, Katsuhiko, Kriebel, Jennifer, Kronenberg, Florian, Kuusisto, Johanna, Lall, Kristi, Lange, Leslie A., Lee, Myung-Shik, Lee, Nanette R., Leong, Aaron, Li, Liming, Li, Yun, Li-Gao, Ruifang, Ligthart, Symen, Lindgren, Cecilia M., Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Locke, Adam E., Louie, Tin, Luan, Jian'an, Luk, Andrea O., Luo, Xi, Lv, Jun, Lyssenko, Valeriya, Mamakou, Vasiliki, Mani, K. Radha, Meitinger, Thomas, Metspalu, Andres, Morris, Andrew D., Nadkarni, Girish N., Nadler, Jerry L., Nalls, Michael A., Nayak, Uma, Nongmaithem, Suraj S., Ntalla, Ioanna, Okada, Yukinori, Orozco, Lorena, Patel, Sanjay R., Pereira, Mark A., Peters, Annette, Pirie, Fraser J., Porneala, Bianca, Prasad, Gauri, Preissl, Sebastian, Rasmussen-Torvik, Laura J., Reiner, Alexander P., Roden, Michael, Rohde, Rebecca, Roll, Kathryn, Sabanayagam, Charumathi, Sander, Maike, Sandow, Kevin, Sattar, Naveed, Schonherr, Sebastian, Schurmann, Claudia, Shahriar, Mohammad, Shi, Jinxiu, Shin, Dong Mun, Shriner, Daniel, Smith, Jennifer A., So, Wing Yee, Stancakova, Alena, Stilp, Adrienne M., Strauch, Konstantin, Suzuki, Ken, Takahashi, Atsushi, Taylor, Kent D., Thorand, Barbara, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tomlinson, Brian, Torres, Jason M., Tsai, Fuu-Jen, Tuomilehto, Jaakko, Tusie-Luna, Teresa, Udler, Miriam S., Valladares-Salgado, Adan, van Dam, Rob M., van Klinken, Jan B., Varma, Rohit, Vujkovic, Marijana, Wacher-Rodarte, Niels, Wheeler, Eleanor, Whitsel, Eric A., Wickremasinghe, Ananda R., van Dijk, Ko Willems, Witte, Daniel R., Yajnik, Chittaranjan S., Yamamoto, Ken, Yamauchi, Toshimasa, Yengo, Loic, Yoon, Kyungheon, Yu, Canqing, Yuan, Jian-Min, Yusuf, Salim, Zhang, Liang, Zheng, Wei, Raffel, Leslie J., Igase, Michiya, Ipp, Eli, Redline, Susan, Cho, Yoon Shin, Lind, Lars, Province, Michael A., Hanis, Craig L., Peyser, Patricia A., Ingelsson, Erik, Zonderman, Alan B., Psaty, Bruce M., Wang, Ya-Xing, Rotimi, Charles N., Becker, Diane M., Matsuda, Fumihiko, Liu, Yongmei, Zeggini, Eleftheria, Yokota, Mitsuhiro, Rich, Stephen S., Kooperberg, Charles, Pankow, James S., Engert, James C., Chen, Yii-Der Ida, Froguel, Philippe, Wilson, James G., Sheu, Wayne H. H., Kardia, Sharon L. R., Wu, Jer-Yuarn, Hayes, M. Geoffrey, Ma, Ronald C. W., Wong, Tien-Yin, Groop, Leif, Mook-Kanamori, Dennis O., Chandak, Giriraj R., Collins, Francis S., Bharadwaj, Dwaipayan, Pare, Guillaume, Sale, Michele M., Ahsan, Habibul, Motala, Ayesha A., Shu, Xiao-Ou, Park, Kyong-Soo, Jukema, J. Wouter, Cruz, Miguel, McKean-Cowdin, Roberta, Grallert, Harald, Cheng, Ching-Yu, Bottinger, Erwin P., Dehghan, Abbas, Tai, E-Shyong, Dupuis, Josee, Kato, Norihiro, Laakso, Markku, Kottgen, Anna, Koh, Woon-Puay, Palmer, Colin N. A., Liu, Simin, Abecasis, Goncalo, Kooner, Jaspal S., Loos, Ruth J. F., North, Kari E., Haiman, Christopher A., Florez, Jose C., Saleheen, Danish, Hansen, Torben, Pedersen, Oluf, Magi, Reedik, Langenberg, Claudia, Wareham, Nicholas J., Maeda, Shiro, Kadowaki, Takashi, Lee, Juyoung, Millwood, Iona Y., Walters, Robin G., Stefansson, Kari, Myers, Simon R., Ferrer, Jorge, Gaulton, Kyle J., Meigs, James B., Mohlke, Karen L., Gloyn, Anna L., Bowden, Donald W., Below, Jennifer E., Chambers, John C., Sim, Xueling, Boehnke, Michael, Rotter, Jerome, I, McCarthy, Mark, I, and Morris, Andrew P.

Abstract

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results