Founder population-specific weights yield improvements in performance of polygenic risk scores for Alzheimer disease in the Midwestern Amish.
Founder population-specific weights yield improvements in performance of polygenic risk scores for Alzheimer disease in the Midwestern Amish.
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DOI：
10.1016/j.xhgg.2023.100241
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发表时间：
2023-10-12
期刊：
影响因子：
--
通讯作者：
Haines, Jonathan L.
中科院分区：
文献类型：
--
作者：
Osterman, Michael D.;Song, Yeunjoo E.;Lynn, Audrey;Miskimen, Kristy;Adams, Larry D.;Laux, Renee A.;Caywood, Laura J.;Prough, Michael B.;Clouse, Jason E.;Herington, Sharlene D.;Slifer, Susan H.;Fuzzell, Sarada L.;Hochstetler, Sherri D.;Main, Leighanne R.;Dorfsman, Daniel A.;Zaman, Andrew F.;Ogrocki, Paula;Lerner, Alan J.;Vance, Jeffery M.;Cuccaro, Michael L.;Scott, William K.;Pericak-Vance, Margaret A.;Haines, Jonathan L.
阿尔茨海默病（AD）是最常见的一种痴呆症，估计有600万美国人受到影响。AD的风险是多因素的，包括遗传和环境风险因素。阿尔茨海默病基因组研究通常侧重于识别风险变异。利用这些信息，可以计算出多基因风险评分（prs），以量化遗传因素导致的个体相对疾病风险。阿米什人是德国和瑞士再洗礼派移民的后裔。他们在到达美国后经历了遗传瓶颈，使他们的基因结构与更广泛的欧洲血统人群不同。先前的工作表明，prs在人群中缺乏可转移性。在这里，我们比较了阿米什个体的全基因组关联研究（GWASs）与来自欧洲祖先GWAS的PRSs的表现。对参与者进行认知障碍筛查，并进一步评估AD。收集后通过Illumina基因分型阵列进行基因型数据的输入。根据招募的主要地点，阿米什人被分成两组。对每一组进行GWAS，考虑相关性和协变量的调整。然后使用另一组阿米什人的权重来计算prs。用协变量和不含协变量对PRS模型进行评估。在我们的阿米什人群中，阿米什衍生的PRS比欧洲衍生的PRS更好地区分了痴呆状态，尽管训练样本量较小，但表现出了性能上的改善。这项工作强调了在不能通过基本种族/民族或祖先分类充分描述的人群中使用AD PRS的考虑。我们发现，使用阿米什衍生效应估计，与广泛的欧洲祖先衍生效应估计相反，在我们的阿米什研究人群中，对阿尔茨海默病的预测能力更强。这突出表明，在进行多基因风险评分分析时，需要适当匹配训练和测试数据，而不是种族/民族类别。
Alzheimer disease (AD) is the most common type of dementia and is estimated to affect 6 million Americans. Risk for AD is multifactorial, including both genetic and environmental risk factors. AD genomic research has generally focused on identification of risk variants. Using this information, polygenic risk scores (PRSs) can be calculated to quantify an individual’s relative disease risk due to genetic factors. The Amish are a founder population descended from German and Swiss Anabaptist immigrants. They experienced a genetic bottleneck after arrival in the United States, making their genetic architecture different from the broader European ancestry population. Prior work has demonstrated the lack of transferability of PRSs across populations. Here, we compared the performance of PRSs derived from genome-wide association studies (GWASs) of Amish individuals to those derived from a large European ancestry GWAS. Participants were screened for cognitive impairment with further evaluation for AD. Genotype data were imputed after collection via Illumina genotyping arrays. The Amish individuals were split into two groups based on the primary site of recruitment. For each group, GWAS was conducted with account for relatedness and adjustment for covariates. PRSs were then calculated using weights from the other Amish group. PRS models were evaluated with and without covariates. The Amish-derived PRSs distinguished between dementia status better than the European-derived PRS in our Amish populations and demonstrated performance improvements despite a smaller training sample size. This work highlighted considerations for AD PRS usage in populations that cannot be adequately described by basic race/ethnicity or ancestry classifications. We found that use of Amish-derived effect estimates, as opposed to broad European ancestry-derived effect estimates, yielded greater predictive ability of Alzheimer disease in our Amish study population. This highlights the need for proper matching of training and testing data beyond race/ethnicity categories when performing polygenic risk score analysis.
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影响因子：
5.8
作者：
Gogarten, Stephanie M.;Sofer, Tamar;Conomos, Matthew P.
通讯作者：
Conomos, Matthew P.
影响因子：
30.8
作者：
Bellenguez, Celine;Kucukali, Fahri;Jansen, Iris E.;Kleineidam, Luca;Moreno-Grau, Sonia;Amin, Najaf;Naj, Adam C.;Campos-Martin, Rafael;Grenier-Boley, Benjamin;Andrade, Victor;Holmans, Peter A.;Boland, Anne;Damotte, Vincent;van der Lee, Sven J.;Costa, Marcos R.;Kuulasmaa, Teemu;Yang, Qiong;De Rojas, Itziar;Bis, Joshua C.;Yaqub, Amber;Prokic, Ivana;Chapuis, Julien;Ahmad, Shahzad;Giedraitis, Vilmantas;Aarsland, Dag;Garcia-Gonzalez, Pablo;Abdelnour, Carla;Alarcon-Martin, Emilio;Alcolea, Daniel;Alegret, Montserrat;Alvarez, Ignacio;Alvarez, Victoria;Armstrong, Nicola J.;Tsolaki, Anthoula;Antunez, Carmen;Appollonio, Ildebrando;Arcaro, Marina;Archetti, Silvana;Arias Pastor, Alfonso;Arosio, Beatrice;Athanasiu, Lavinia;Bailly, Henri;Banaj, Nerisa;Baquero, Miquel;Barral, Sandra;Beiser, Alexa;Pastor, Ana Belen;Below, Jennifer E.;Benchek, Penelope;Benussi, Luisa;Berr, Claudine;Besse, Celine;Bessi, Valentina;Binetti, Giuliano;Bizarro, Alessandra;Blesa, Rafael;Boada, Merce;Boerwinkle, Eric;Borroni, Barbara;Boschi, Silvia;Bossu, Paola;Brathen, Geir;Bressler, Jan;Bresner, Catherine;Brodaty, Henry;Brookes, Keeley J.;Ignacio Brusco, Luis;Buiza-Rueda, Dolores;Burger, Katharina;Burholt, Vanessa;Bush, William S.;Calero, Miguel;Cantwell, Laura B.;Chene, Genevieve;Chung, Jaeyoon;Cuccaro, Michael L.;Cecchetti, Roberta;Cervera-Carles, Laura;Charbonnier, Camille;Chen, Hung-Hsin;Chillotti, Caterina;Ciccone, Simona;Claassen, Jurgen A. H. R.;Clark, Christopher;Conti, Elisa;Corma-Gomez, Anais;Costantini, Emanuele;Custodero, Carlo;Daian, Delphine;Dalmasso, Maria Carolina;Daniele, Antonio;Dardiotis, Efthimios;Dartigues, Jean-Francois;de Deyn, Peter Paul;Lopes, Katia de Paiva;De Witte, Lot D.;Debette, Stephanie;Deckert, Jurgen;del Ser, Teodoro;Denning, Nicola;Destefano, Anita;Dichgans, Martin;Diehl-Schmid, Janine;Diez-Fairen, Monica;Rossi, Paolo Dionigi;Djurovic, Srdjan;Duron, Emmanuelle;Duzel, Emrah;Dufouil, Carole;Eiriksdottir, Gudny;Engelborghs, Sebastiaan;Escott-Price, Valentina;Espinosa, Ana;Ewers, Michael;Faber, Kelley M.;Fabrizio, Tagliavini;Nielsen, Sune Fallgaard;Fardo, David W.;Farotti, Lucia;Fenoglio, Chiara;Fernandez-Fuertes, Marta;Ferrari, Raffaele;Ferreira, Catarina B.;Ferri, Evelyn;Fin, Bertrand;Fischer, Peter;Fladby, Tormod;Fliessbach, Klaus;Fongang, Bernard;Fornage, Myriam;Fortea, Juan;Foroud, Tatiana M.;Fostinelli, Silvia;Fox, Nick C.;Franco-Macias, Emlio;Bullido, Maria J.;Frank-Garcia, Ana;Froelich, Lutz;Fulton-Howard, Brian;Galimberti, Daniela;Maria Garcia-Alberca, Jose;Garcia-Madrona, Sebastian;Garcia-Ribas, Guillermo;Ghidoni, Roberta;Giegling, Ina;Giorgio, Giaccone;Goate, Alison M.;Goldhardt, Oliver;Gomez-Fonseca, Duber;Gonzalez-Perez, Antonio;Graff, Caroline;Grande, Giulia;Green, Emma;Grimmer, Timo;Grunblatt, Edna;Grunin, Michelle;Gudnason, Vilmundur;Guetta-Baranes, Tamar;Haapasalo, Annakaisa;Hadjigeorgiou, Georgios;Haines, Jonathan L.;Hamilton-Nelson, Kara L.;Hampel, Harald;Hanon, Olivier;Hardy, John;Hartmann, Annette M.;Hausner, Lucrezia;Harwood, Janet;Heilmann-Heimbach, Stefanie;Helisalmi, Seppo;Heneka, Michael T.;Hernandez, Isabel;Herrmann, Martin J.;Hoffmann, Per;Holmes, Clive;Holstege, Henne;Huerto Vilas, Raquel;Hulsman, Marc;Humphrey, Jack;Biessels, Geert Jan;Jian, Xueqiu;Johansson, Charlotte;Jun, Gyungah R.;Kastumata, Yuriko;Kauwe, John;Kehoe, Patrick G.;Kilander, Lena;Stahlbom, Anne Kinhult;Kivipelto, Miia;Koivisto, Anne;Kornhuber, Johannes;Kosmidis, Mary H.;Kukull, Walter A.;Kuksa, Pavel P.;Kunkle, Brian W.;Kuzma, Amanda B.;Lage, Carmen;Laukka, Erika J.;Launer, Lenore;Lauria, Alessandra;Lee, Chien-Yueh;Lehtisalo, Jenni;Lerch, Ondrej;Lleo, Alberto;Longstreth, William, Jr.;Lopez, Oscar;Lopez de Munain, Adolfo;Love, Seth;Lowemark, Malin;Luckcuck, Lauren;Lunetta, Kathryn L.;Ma, Yiyi;Macias, Juan;Macleod, Catherine A.;Maier, Wolfgang;Mangialasche, Francesca;Spallazzi, Marco;Marquie, Marta;Marshall, Rachel;Martin, Eden R.;Martin Montes, Angel;Martinez Rodriguez, Carmen;Masullo, Carlo;Mayeux, Richard;Mead, Simon;Mecocci, Patrizia;Medina, Miguel;Meggy, Alun;Mehrabian, Shima;Mendoza, Silvia;Menendez-Gonzalez, Manuel;Mir, Pablo;Moebus, Susanne;Mol, Merel;Molina-Porcel, Laura;Montrreal, Laura;Morelli, Laura;Moreno, Fermin;Morgan, Kevin;Mosley, Thomas;Nothen, Markus M.;Muchnik, Carolina;Mukherjee, Shubhabrata;Nacmias, Benedetta;Ngandu, Tiia;Nicolas, Gael;Nordestgaard, Borge G.;Olaso, Robert;Orellana, Adelina;Orsini, Michela;Ortega, Gemma;Padovani, Alessandro;Paolo, Caffarra;Papenberg, Goran;Parnetti, Lucilla;Pasquier, Florence;Pastor, Pau;Peloso, Gina;Perez-Cordon, Alba;Perez-Tur, Jordi;Pericard, Pierre;Peters, Oliver;Pijnenburg, Yolande A. L.;Pineda, Juan A.;Pinol-Ripoll, Gerard;Pisanu, Laudia;Polak, Thomas;Popp, Julius;Posthuma, Danielle;Priller, Josef;Puerta, Raquel;Quenez, Olivier;Quintela, Ines;Thomassen, Jesper Qvist;Rabano, Alberto;Rainero, Innocenzo;Rajabli, Farid;Ramakers, Inez;Real, Luis M.;Reinders, Marcel J. T.;Reitz, Christiane;Reyes-Dumeyer, Dolly;Ridge, Perry;Riedel-Heller, Steffi;Riederer, Peter;Roberto, Natalia;Rodriguez-Rodriguez, Eloy;Rongve, Arvid;Rosas Allende, Irene;Rosende-Roca, Maitee;Luis Royo, Jose;Rubino, Elisa;Rujescu, Dan;Eugenia Saez, Maria;Sakka, Paraskevi;Saltvedt, Ingvild;Bernal Sanchez-Arjona, Maria;Sanchez-Garcia, Florentino;Sanchez Juan, Pascual;Sanchez-Valle, Raquel;Sando, Sigrid B.;Sarnowski, Chloe;Satizabal, Claudia L.;Scamosci, Michela;Scarmeas, Nikolaos;Scarpini, Elio;Scheltens, Philip;Scherbaum, Norbert;Scherer, Martin;Schmid, Matthias;Schneider, Anja;Schott, Jonathan M.;Selbaek, Geir;Seripa, Davide;Serrano, Manuel;Sha, Jin;Shadrin, Alexey A.;Skrobot, Olivia;Slifer, Susan;Snijders, Gijsje J. L.;Soininen, Hilkka;Solfrizzi, Vincenzo;Solomon, Alina;Song, Yeunjoo;Sorbi, Sandro;Sotolongo-Grau, Oscar;Spalletta, Gianfranco;Spottke, Annika;Squassina, Alessio;Stordal, Eystein;Pablo Tartan, Juan;Tarraga, Lluis;Tesi, Niccolo;Thalamuthu, Anbupalam;Thomas, Tegos;Tosto, Giuseppe;Traykov, Latchezar;Tremolizzo, Lucio;Tybjaerg-Hansen, Anne;Uitterlinden, Andre;Ullgren, Abbe;Ulstein, Ingun;Valero, Sergi;Valladares, Otto;Van Broeckhoven, Christine;Vance, Jeffery;Vardarajan, Badri N.;van der Lugt, Aad;Van Dongen, Jasper;van Rooij, Jeroen;van Swieten, John;Vandenberghe, Rik;Verhey, Frans;Vidal, Jean-Sebastien;Vogelgsang, Jonathan;Vyhnalek, Martin;Wagner, Michael;Wallon, David;Wang, Li-San;Wang, Ruiqi;Weinhold, Leonie;Wiltfang, Jens;Windle, Gill;Woods, Bob;Yannakoulia, Mary;Zare, Habil;Zhao, Yi;Zhang, Xiaoling;Zhu, Congcong;Zulaica, Miren;Farrer, Lindsay A.;Psaty, Bruce M.;Ghanbari, Mohsen;Raj, Towfique;Sachdev, Perminder;Mather, Karen;Jessen, Frank;Ikram, M. Arfan;de Mendonca, Alexandre;Hort, Jakub;Tsolaki, Magda;Pericak-Vance, Margaret A.;Amouyel, Philippe;Williams, Julie;Frikke-Schmidt, Ruth;Clarimon, Jordi;Deleuze, Jean-Francois;Rossi, Giacomina;Seshadri, Sudha;Andreassen, Ole A.;Ingelsson, Martin;Hiltunen, Mikko;Sleegers, Kristel;Schellenberg, Gerard D.;van Duijn, Cornelia M.;Sims, Rebecca;van der Flier, Wiesje M.;Ruiz, Agustin;Ramirez, Alfredo;Lambert, Jean-Charles
通讯作者：
Lambert, Jean-Charles
DOI：
10.1016/j.xhgg.2022.100114
发表时间：
2022-07-14
期刊：
HUMAN GENETICS AND GENOMICS ADVANCES
影响因子：
--
作者：
Osterman, Michael D.;Song, Yeunjoo E.;Adams, Larry D.;Laux, Renee A.;Caywood, Laura J.;Prough, Michael B.;Clouse, Jason E.;Herington, Sharlene D.;Slifer, Susan H.;Lynn, Audrey;Fuzzell, M. Denise;Fuzzell, Sarada L.;Hochstetler, Sherri D.;Miskimen, Kristy;Main, Leighanne R.;Dorfsman, Daniel A.;Ogrocki, Paula;Lerner, Alan J.;Ramos, Jairo;Vance, Jeffery M.;Cuccaro, Michael L.;Scott, William K.;Pericak-Vance, Margaret A.;Haines, Jonathan L.
通讯作者：
Haines, Jonathan L.
影响因子：
5.3
作者：
Courtenay MD;Gilbert JR;Jiang L;Cummings AC;Gallins PJ;Caywood L;Reinhart-Mercer L;Fuzzell D;Knebusch C;Laux R;McCauley JL;Jackson CE;Pericak-Vance MA;Haines JL;Scott WK
通讯作者：
Scott WK
影响因子：
16.6
作者：
Duncan, L.;Shen, H.;Domingue, B.
通讯作者：
Domingue, B.