Wu Y, Sun Z, Zheng Q, Miao J, Dorn S, Mukherjee S, Fletcher JM, Lu Q.
Pervasive biases in proxy genome-wide association studies based on parental history of Alzheimer's disease.
Nat Genet. 2024 Dec;56(12):2696-2703. Epub 2024 Nov 4
PubMed.
Genome-wide association studies on Alzheimer’s disease and related dementias mainly focus on the identification of new genetic risk factors for ADRD. Performing a GWAX, i.e., a GWAS on proxy ADRD cases (i.e. individuals reporting at least one parent with dementia), and meta-analyzing the results with GWAS on clinically diagnosed AD cases (GWAS+GWAX meta-analysis) allows us to greatly increase GWAS discovery power. Even if GWAX tend to underestimate effect sizes, effects of the reported genome-wide significant variants are similar in GWAS+GWAX and in GWAS, supporting the validity of the strategy.
While GWAS focus mainly on genome-wide significant variants, the genome-wide summary statistics have to be made publicly available, and results of variants not reaching genome-wide significance are used to perform many other kinds of genetic analyses. However, assumptions of classical genetic approaches may not be met by summary statistics of GWAS+GWAX. For example, heritability values are underestimated if the inclusion of proxy cases is not properly accounted for (de la Fuente et al., 2022) and spurious associations between longer educational attainment and higher AD risk are observed in Mendelian randomization studies (Liu et al., 2022; EADB-MR Collaboration, 2023). Due to these biases, researchers perform sensitivity analyses of their GWAX-based results using GWAS summary statistics.
Here, Wu et al. confirm biases in results of some analyses performed on GWAX or GWAS+GWAX genome-wide summary statistics. They go further by identifying different mechanisms leading to those biases, and compare different strategies to improve GWAX. Of note, the sources of bias identified by the authors, such as survival bias and nonrandom participation, may also affect classical GWAS, particularly in large-scale biobanks. Developing methodological approaches dedicated to GWAX and to large-scale biobank GWAS is of great importance. This can minimize biases in analyses of genome-wide summary statistics from GWAS+GWAX, especially as GWAX and biobank GWAS results are expected to outweigh clinically diagnosed AD GWAS results in future GWAS+GWAX.
Additionally, novel genome-wide significant variants are expected to be rarer or to have low effect size, but classical GWAX correction factors were developed for variants with a moderate-to-high frequency only. Additionally, the biases reported by Wu et al. affect variants with low effect size, and might thus impact genome-wide significant variants, too, in the future. Methodological development should go along with GWAS on further well-characterized AD patients and functional studies to assess sensitivity and validate the genetic findings of ADRD GWAS+GWAX.
References:
de la Fuente J, Grotzinger AD, Marioni RE, Nivard MG, Tucker-Drob EM.
Integrated analysis of direct and proxy genome wide association studies highlights polygenicity of Alzheimer's disease outside of the APOE region.
PLoS Genet. 2022 Jun;18(6):e1010208. Epub 2022 Jun 3
PubMed.
Liu H, Hu Y, Zhang Y, Zhang H, Gao S, Wang L, Wang T, Han Z, Sun BL, Liu G.
Mendelian randomization highlights significant difference and genetic heterogeneity in clinically diagnosed Alzheimer's disease GWAS and self-report proxy phenotype GWAX.
Alzheimers Res Ther. 2022 Jan 28;14(1):17.
PubMed.
European Alzheimer’s & Dementia Biobank Mendelian Randomization (EADB-MR) Collaboration, Luo J, Thomassen JQ, Bellenguez C, Grenier-Boley B, de Rojas I, Castillo A, Parveen K, Küçükali F, Nicolas A, Peters O, Schneider A, Dichgans M, Rujescu D, Scherbaum N, Jürgen D, Riedel-Heller S, Hausner L, Porcel LM, Düzel E, Grimmer T, Wiltfang J, Heilmann-Heimbach S, Moebus S, Tegos T, Scarmeas N, Clarimon J, Moreno F, Pérez-Tur J, Bullido MJ, Pastor P, Sánchez-Valle R, Álvarez V, Boada M, García-González P, Puerta R, Mir P, Real LM, Piñol-Ripoll G, García-Alberca JM, Royo JL, Rodriguez-Rodriguez E, Soininen H, Kuulasmaa T, de Mendonça A, Mehrabian S, Hort J, Vyhnalek M, van der Lee S, Graff C, Papenberg G, Giedraitis V, Boland A, Bacq-Daian D, Deleuze JF, Nicolas G, Dufouil C, Pasquier F, Hanon O, Debette S, Grünblatt E, Popp J, Benussi L, Galimberti D, Arosio B, Mecocci P, Solfrizzi V, Parnetti L, Squassina A, Tremolizzo L, Borroni B, Nacmias B, Sorbi S, Caffarra P, Seripa D, Rainero I, Daniele A, Masullo C, Spalletta G, Williams J, Amouyel P, Jessen F, Kehoe P, Magda T, Rossi G, Sánchez-Juan P, Sleegers K, Ingelsson M, Andreassen OA, Hiltunen M, Van Duijn C, Sims R, van der Flier W, Ruiz A, Ramirez A, Lambert JC, Frikke-Schmidt R.
Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease.
JAMA Netw Open. 2023 May 1;6(5):e2313734.
PubMed.
Yes, we agree with these critiques. In fact, when Nature Genetics accepted the proxy “AD” GWAS paper, we wrote saying it had been poorly reviewed (Bellenguez et al., 2022). A better title for the original paper would have been “A Proxy GWAS for Reported Dementia” rather than Alzheimer’s disease, and we noted that, in addition to these critiques, FTD genes were showing up in the “AD” GWAS. Our critique was rebuffed, but modified it became 'bigger is not better' (Escott-Price and Hardy, 2022).
References:
Bellenguez C, Küçükali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N, Naj AC, Campos-Martin R, Grenier-Boley B, Andrade V, Holmans PA, Boland A, Damotte V, van der Lee SJ, Costa MR, Kuulasmaa T, Yang Q, de Rojas I, Bis JC, Yaqub A, Prokic I, Chapuis J, Ahmad S, Giedraitis V, Aarsland D, Garcia-Gonzalez P, Abdelnour C, Alarcón-Martín E, Alcolea D, Alegret M, Alvarez I, Álvarez V, Armstrong NJ, Tsolaki A, Antúnez C, Appollonio I, Arcaro M, Archetti S, Pastor AA, Arosio B, Athanasiu L, Bailly H, Banaj N, Baquero M, Barral S, Beiser A, Pastor AB, Below JE, Benchek P, Benussi L, Berr C, Besse C, Bessi V, Binetti G, Bizarro A, Blesa R, Boada M, Boerwinkle E, Borroni B, Boschi S, Bossù P, Bråthen G, Bressler J, Bresner C, Brodaty H, Brookes KJ, Brusco LI, Buiza-Rueda D, Bûrger K, Burholt V, Bush WS, Calero M, Cantwell LB, Chene G, Chung J, Cuccaro ML, Carracedo Á, Cecchetti R, Cervera-Carles L, Charbonnier C, Chen HH, Chillotti C, Ciccone S, Claassen JA, Clark C, Conti E, Corma-Gómez A, Costantini E, Custodero C, Daian D, Dalmasso MC, Daniele A, Dardiotis E, Dartigues JF, de Deyn PP, de Paiva Lopes K, de Witte LD, Debette S, Deckert J, Del Ser T, Denning N, DeStefano A, Dichgans M, Diehl-Schmid J, Diez-Fairen M, Rossi PD, Djurovic S, Duron E, Düzel E, Dufouil C, Eiriksdottir G, Engelborghs S, Escott-Price V, Espinosa A, Ewers M, Faber KM, Fabrizio T, Nielsen SF, Fardo DW, Farotti L, Fenoglio C, Fernández-Fuertes M, Ferrari R, Ferreira CB, Ferri E, Fin B, Fischer P, Fladby T, Fließbach K, Fongang B, Fornage M, Fortea J, Foroud TM, Fostinelli S, Fox NC, Franco-Macías E, Bullido MJ, Frank-García A, Froelich L, Fulton-Howard B, Galimberti D, García-Alberca JM, García-González P, Garcia-Madrona S, Garcia-Ribas G, Ghidoni R, Giegling I, Giorgio G, Goate AM, Goldhardt O, Gomez-Fonseca D, González-Pérez A, Graff C, Grande G, Green E, Grimmer T, Grünblatt E, Grunin M, Gudnason V, Guetta-Baranes T, Haapasalo A, Hadjigeorgiou G, Haines JL, Hamilton-Nelson KL, Hampel H, Hanon O, Hardy J, Hartmann AM, Hausner L, Harwood J, Heilmann-Heimbach S, Helisalmi S, Heneka MT, Hernández I, Herrmann MJ, Hoffmann P, Holmes C, Holstege H, Vilas RH, Hulsman M, Humphrey J, Biessels GJ, Jian X, Johansson C, Jun GR, Kastumata Y, Kauwe J, Kehoe PG, Kilander L, Ståhlbom AK, Kivipelto M, Koivisto A, Kornhuber J, Kosmidis MH, Kukull WA, Kuksa PP, Kunkle BW, Kuzma AB, Lage C, Laukka EJ, Launer L, Lauria A, Lee CY, Lehtisalo J, Lerch O, Lleó A, Longstreth W Jr, Lopez O, de Munain AL, Love S, Löwemark M, Luckcuck L, Lunetta KL, Ma Y, Macías J, MacLeod CA, Maier W, Mangialasche F, Spallazzi M, Marquié M, Marshall R, Martin ER, Montes AM, Rodríguez CM, Masullo C, Mayeux R, Mead S, Mecocci P, Medina M, Meggy A, Mehrabian S, Mendoza S, Menéndez-González M, Mir P, Moebus S, Mol M, Molina-Porcel L, Montrreal L, Morelli L, Moreno F, Morgan K, Mosley T, Nöthen MM, Muchnik C, Mukherjee S, Nacmias B, Ngandu T, Nicolas G, Nordestgaard BG, Olaso R, Orellana A, Orsini M, Ortega G, Padovani A, Paolo C, Papenberg G, Parnetti L, Pasquier F, Pastor P, Peloso G, Pérez-Cordón A, Pérez-Tur J, Pericard P, Peters O, Pijnenburg YA, Pineda JA, Piñol-Ripoll G, Pisanu C, Polak T, Popp J, Posthuma D, Priller J, Puerta R, Quenez O, Quintela I, Thomassen JQ, Rábano A, Rainero I, Rajabli F, Ramakers I, Real LM, Reinders MJ, Reitz C, Reyes-Dumeyer D, Ridge P, Riedel-Heller S, Riederer P, Roberto N, Rodriguez-Rodriguez E, Rongve A, Allende IR, Rosende-Roca M, Royo JL, Rubino E, Rujescu D, Sáez ME, Sakka P, Saltvedt I, Sanabria Á, Sánchez-Arjona MB, Sanchez-Garcia F, Juan PS, Sánchez-Valle R, Sando SB, Sarnowski C, Satizabal CL, Scamosci M, Scarmeas N, Scarpini E, Scheltens P, Scherbaum N, Scherer M, Schmid M, Schneider A, Schott JM, Selbæk G, Seripa D, Serrano M, Sha J, Shadrin AA, Skrobot O, Slifer S, Snijders GJ, Soininen H, Solfrizzi V, Solomon A, Song Y, Sorbi S, Sotolongo-Grau O, Spalletta G, Spottke A, Squassina A, Stordal E, Tartan JP, Tárraga L, Tesí N, Thalamuthu A, Thomas T, Tosto G, Traykov L, Tremolizzo L, Tybjærg-Hansen A, Uitterlinden A, Ullgren A, Ulstein I, Valero S, Valladares O, Broeckhoven CV, Vance J, Vardarajan BN, van der Lugt A, Dongen JV, van Rooij J, van Swieten J, Vandenberghe R, Verhey F, Vidal JS, Vogelgsang J, Vyhnalek M, Wagner M, Wallon D, Wang LS, Wang R, Weinhold L, Wiltfang J, Windle G, Woods B, Yannakoulia M, Zare H, Zhao Y, Zhang X, Zhu C, Zulaica M, EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Farrer LA, Psaty BM, Ghanbari M, Raj T, Sachdev P, Mather K, Jessen F, Ikram MA, de Mendonça A, Hort J, Tsolaki M, Pericak-Vance MA, Amouyel P, Williams J, Frikke-Schmidt R, Clarimon J, Deleuze JF, Rossi G, Seshadri S, Andreassen OA, Ingelsson M, Hiltunen M, Sleegers K, Schellenberg GD, van Duijn CM, Sims R, van der Flier WM, Ruiz A, Ramirez A, Lambert JC.
New insights into the genetic etiology of Alzheimer's disease and related dementias.
Nat Genet. 2022 Apr;54(4):412-436. Epub 2022 Apr 4
PubMed.
Escott-Price V, Hardy J.
Genome-wide association studies for Alzheimer's disease: bigger is not always better.
Brain Commun. 2022;4(3):fcac125. Epub 2022 May 17
PubMed.
Comments
University of Lille, Inserm, Institute Pasteur Lille
Genome-wide association studies on Alzheimer’s disease and related dementias mainly focus on the identification of new genetic risk factors for ADRD. Performing a GWAX, i.e., a GWAS on proxy ADRD cases (i.e. individuals reporting at least one parent with dementia), and meta-analyzing the results with GWAS on clinically diagnosed AD cases (GWAS+GWAX meta-analysis) allows us to greatly increase GWAS discovery power. Even if GWAX tend to underestimate effect sizes, effects of the reported genome-wide significant variants are similar in GWAS+GWAX and in GWAS, supporting the validity of the strategy.
While GWAS focus mainly on genome-wide significant variants, the genome-wide summary statistics have to be made publicly available, and results of variants not reaching genome-wide significance are used to perform many other kinds of genetic analyses. However, assumptions of classical genetic approaches may not be met by summary statistics of GWAS+GWAX. For example, heritability values are underestimated if the inclusion of proxy cases is not properly accounted for (de la Fuente et al., 2022) and spurious associations between longer educational attainment and higher AD risk are observed in Mendelian randomization studies (Liu et al., 2022; EADB-MR Collaboration, 2023). Due to these biases, researchers perform sensitivity analyses of their GWAX-based results using GWAS summary statistics.
Here, Wu et al. confirm biases in results of some analyses performed on GWAX or GWAS+GWAX genome-wide summary statistics. They go further by identifying different mechanisms leading to those biases, and compare different strategies to improve GWAX. Of note, the sources of bias identified by the authors, such as survival bias and nonrandom participation, may also affect classical GWAS, particularly in large-scale biobanks. Developing methodological approaches dedicated to GWAX and to large-scale biobank GWAS is of great importance. This can minimize biases in analyses of genome-wide summary statistics from GWAS+GWAX, especially as GWAX and biobank GWAS results are expected to outweigh clinically diagnosed AD GWAS results in future GWAS+GWAX.
Additionally, novel genome-wide significant variants are expected to be rarer or to have low effect size, but classical GWAX correction factors were developed for variants with a moderate-to-high frequency only. Additionally, the biases reported by Wu et al. affect variants with low effect size, and might thus impact genome-wide significant variants, too, in the future. Methodological development should go along with GWAS on further well-characterized AD patients and functional studies to assess sensitivity and validate the genetic findings of ADRD GWAS+GWAX.
References:
de la Fuente J, Grotzinger AD, Marioni RE, Nivard MG, Tucker-Drob EM. Integrated analysis of direct and proxy genome wide association studies highlights polygenicity of Alzheimer's disease outside of the APOE region. PLoS Genet. 2022 Jun;18(6):e1010208. Epub 2022 Jun 3 PubMed.
Liu H, Hu Y, Zhang Y, Zhang H, Gao S, Wang L, Wang T, Han Z, Sun BL, Liu G. Mendelian randomization highlights significant difference and genetic heterogeneity in clinically diagnosed Alzheimer's disease GWAS and self-report proxy phenotype GWAX. Alzheimers Res Ther. 2022 Jan 28;14(1):17. PubMed.
European Alzheimer’s & Dementia Biobank Mendelian Randomization (EADB-MR) Collaboration, Luo J, Thomassen JQ, Bellenguez C, Grenier-Boley B, de Rojas I, Castillo A, Parveen K, Küçükali F, Nicolas A, Peters O, Schneider A, Dichgans M, Rujescu D, Scherbaum N, Jürgen D, Riedel-Heller S, Hausner L, Porcel LM, Düzel E, Grimmer T, Wiltfang J, Heilmann-Heimbach S, Moebus S, Tegos T, Scarmeas N, Clarimon J, Moreno F, Pérez-Tur J, Bullido MJ, Pastor P, Sánchez-Valle R, Álvarez V, Boada M, García-González P, Puerta R, Mir P, Real LM, Piñol-Ripoll G, García-Alberca JM, Royo JL, Rodriguez-Rodriguez E, Soininen H, Kuulasmaa T, de Mendonça A, Mehrabian S, Hort J, Vyhnalek M, van der Lee S, Graff C, Papenberg G, Giedraitis V, Boland A, Bacq-Daian D, Deleuze JF, Nicolas G, Dufouil C, Pasquier F, Hanon O, Debette S, Grünblatt E, Popp J, Benussi L, Galimberti D, Arosio B, Mecocci P, Solfrizzi V, Parnetti L, Squassina A, Tremolizzo L, Borroni B, Nacmias B, Sorbi S, Caffarra P, Seripa D, Rainero I, Daniele A, Masullo C, Spalletta G, Williams J, Amouyel P, Jessen F, Kehoe P, Magda T, Rossi G, Sánchez-Juan P, Sleegers K, Ingelsson M, Andreassen OA, Hiltunen M, Van Duijn C, Sims R, van der Flier W, Ruiz A, Ramirez A, Lambert JC, Frikke-Schmidt R. Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease. JAMA Netw Open. 2023 May 1;6(5):e2313734. PubMed.
Institute of Neurology, UCL
Cardiff University
Yes, we agree with these critiques. In fact, when Nature Genetics accepted the proxy “AD” GWAS paper, we wrote saying it had been poorly reviewed (Bellenguez et al., 2022). A better title for the original paper would have been “A Proxy GWAS for Reported Dementia” rather than Alzheimer’s disease, and we noted that, in addition to these critiques, FTD genes were showing up in the “AD” GWAS. Our critique was rebuffed, but modified it became 'bigger is not better' (Escott-Price and Hardy, 2022).
References:
Bellenguez C, Küçükali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N, Naj AC, Campos-Martin R, Grenier-Boley B, Andrade V, Holmans PA, Boland A, Damotte V, van der Lee SJ, Costa MR, Kuulasmaa T, Yang Q, de Rojas I, Bis JC, Yaqub A, Prokic I, Chapuis J, Ahmad S, Giedraitis V, Aarsland D, Garcia-Gonzalez P, Abdelnour C, Alarcón-Martín E, Alcolea D, Alegret M, Alvarez I, Álvarez V, Armstrong NJ, Tsolaki A, Antúnez C, Appollonio I, Arcaro M, Archetti S, Pastor AA, Arosio B, Athanasiu L, Bailly H, Banaj N, Baquero M, Barral S, Beiser A, Pastor AB, Below JE, Benchek P, Benussi L, Berr C, Besse C, Bessi V, Binetti G, Bizarro A, Blesa R, Boada M, Boerwinkle E, Borroni B, Boschi S, Bossù P, Bråthen G, Bressler J, Bresner C, Brodaty H, Brookes KJ, Brusco LI, Buiza-Rueda D, Bûrger K, Burholt V, Bush WS, Calero M, Cantwell LB, Chene G, Chung J, Cuccaro ML, Carracedo Á, Cecchetti R, Cervera-Carles L, Charbonnier C, Chen HH, Chillotti C, Ciccone S, Claassen JA, Clark C, Conti E, Corma-Gómez A, Costantini E, Custodero C, Daian D, Dalmasso MC, Daniele A, Dardiotis E, Dartigues JF, de Deyn PP, de Paiva Lopes K, de Witte LD, Debette S, Deckert J, Del Ser T, Denning N, DeStefano A, Dichgans M, Diehl-Schmid J, Diez-Fairen M, Rossi PD, Djurovic S, Duron E, Düzel E, Dufouil C, Eiriksdottir G, Engelborghs S, Escott-Price V, Espinosa A, Ewers M, Faber KM, Fabrizio T, Nielsen SF, Fardo DW, Farotti L, Fenoglio C, Fernández-Fuertes M, Ferrari R, Ferreira CB, Ferri E, Fin B, Fischer P, Fladby T, Fließbach K, Fongang B, Fornage M, Fortea J, Foroud TM, Fostinelli S, Fox NC, Franco-Macías E, Bullido MJ, Frank-García A, Froelich L, Fulton-Howard B, Galimberti D, García-Alberca JM, García-González P, Garcia-Madrona S, Garcia-Ribas G, Ghidoni R, Giegling I, Giorgio G, Goate AM, Goldhardt O, Gomez-Fonseca D, González-Pérez A, Graff C, Grande G, Green E, Grimmer T, Grünblatt E, Grunin M, Gudnason V, Guetta-Baranes T, Haapasalo A, Hadjigeorgiou G, Haines JL, Hamilton-Nelson KL, Hampel H, Hanon O, Hardy J, Hartmann AM, Hausner L, Harwood J, Heilmann-Heimbach S, Helisalmi S, Heneka MT, Hernández I, Herrmann MJ, Hoffmann P, Holmes C, Holstege H, Vilas RH, Hulsman M, Humphrey J, Biessels GJ, Jian X, Johansson C, Jun GR, Kastumata Y, Kauwe J, Kehoe PG, Kilander L, Ståhlbom AK, Kivipelto M, Koivisto A, Kornhuber J, Kosmidis MH, Kukull WA, Kuksa PP, Kunkle BW, Kuzma AB, Lage C, Laukka EJ, Launer L, Lauria A, Lee CY, Lehtisalo J, Lerch O, Lleó A, Longstreth W Jr, Lopez O, de Munain AL, Love S, Löwemark M, Luckcuck L, Lunetta KL, Ma Y, Macías J, MacLeod CA, Maier W, Mangialasche F, Spallazzi M, Marquié M, Marshall R, Martin ER, Montes AM, Rodríguez CM, Masullo C, Mayeux R, Mead S, Mecocci P, Medina M, Meggy A, Mehrabian S, Mendoza S, Menéndez-González M, Mir P, Moebus S, Mol M, Molina-Porcel L, Montrreal L, Morelli L, Moreno F, Morgan K, Mosley T, Nöthen MM, Muchnik C, Mukherjee S, Nacmias B, Ngandu T, Nicolas G, Nordestgaard BG, Olaso R, Orellana A, Orsini M, Ortega G, Padovani A, Paolo C, Papenberg G, Parnetti L, Pasquier F, Pastor P, Peloso G, Pérez-Cordón A, Pérez-Tur J, Pericard P, Peters O, Pijnenburg YA, Pineda JA, Piñol-Ripoll G, Pisanu C, Polak T, Popp J, Posthuma D, Priller J, Puerta R, Quenez O, Quintela I, Thomassen JQ, Rábano A, Rainero I, Rajabli F, Ramakers I, Real LM, Reinders MJ, Reitz C, Reyes-Dumeyer D, Ridge P, Riedel-Heller S, Riederer P, Roberto N, Rodriguez-Rodriguez E, Rongve A, Allende IR, Rosende-Roca M, Royo JL, Rubino E, Rujescu D, Sáez ME, Sakka P, Saltvedt I, Sanabria Á, Sánchez-Arjona MB, Sanchez-Garcia F, Juan PS, Sánchez-Valle R, Sando SB, Sarnowski C, Satizabal CL, Scamosci M, Scarmeas N, Scarpini E, Scheltens P, Scherbaum N, Scherer M, Schmid M, Schneider A, Schott JM, Selbæk G, Seripa D, Serrano M, Sha J, Shadrin AA, Skrobot O, Slifer S, Snijders GJ, Soininen H, Solfrizzi V, Solomon A, Song Y, Sorbi S, Sotolongo-Grau O, Spalletta G, Spottke A, Squassina A, Stordal E, Tartan JP, Tárraga L, Tesí N, Thalamuthu A, Thomas T, Tosto G, Traykov L, Tremolizzo L, Tybjærg-Hansen A, Uitterlinden A, Ullgren A, Ulstein I, Valero S, Valladares O, Broeckhoven CV, Vance J, Vardarajan BN, van der Lugt A, Dongen JV, van Rooij J, van Swieten J, Vandenberghe R, Verhey F, Vidal JS, Vogelgsang J, Vyhnalek M, Wagner M, Wallon D, Wang LS, Wang R, Weinhold L, Wiltfang J, Windle G, Woods B, Yannakoulia M, Zare H, Zhao Y, Zhang X, Zhu C, Zulaica M, EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Farrer LA, Psaty BM, Ghanbari M, Raj T, Sachdev P, Mather K, Jessen F, Ikram MA, de Mendonça A, Hort J, Tsolaki M, Pericak-Vance MA, Amouyel P, Williams J, Frikke-Schmidt R, Clarimon J, Deleuze JF, Rossi G, Seshadri S, Andreassen OA, Ingelsson M, Hiltunen M, Sleegers K, Schellenberg GD, van Duijn CM, Sims R, van der Flier WM, Ruiz A, Ramirez A, Lambert JC. New insights into the genetic etiology of Alzheimer's disease and related dementias. Nat Genet. 2022 Apr;54(4):412-436. Epub 2022 Apr 4 PubMed.
Escott-Price V, Hardy J. Genome-wide association studies for Alzheimer's disease: bigger is not always better. Brain Commun. 2022;4(3):fcac125. Epub 2022 May 17 PubMed.
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