{"doi":"10.1038/srep44272","title":"Mining Outcome-relevant Brain Imaging Genetic Associations via Three-way Sparse Canonical Correlation Analysis in Alzheimer’s Disease","abstract":"<jats:title>Abstract</jats:title><jats:p>Neuroimaging genetics is an emerging field that aims to identify the associations between genetic variants (e.g., single nucleotide polymorphisms (SNPs)) and quantitative traits (QTs) such as brain imaging phenotypes. In recent studies, in order to detect complex multi-SNP-multi-QT associations, bi-multivariate techniques such as various structured sparse canonical correlation analysis (SCCA) algorithms have been proposed and used in imaging genetics studies. However, associations between genetic markers and imaging QTs identified by existing bi-multivariate methods may not be all disease specific. To bridge this gap, we propose an analytical framework, based on three-way sparse canonical correlation analysis (T-SCCA), to explore the intrinsic associations among genetic markers, imaging QTs, and clinical scores of interest. We perform an empirical study using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort to discover the relationships among SNPs from AD risk gene<jats:italic>APOE</jats:italic>, imaging QTs extracted from structural magnetic resonance imaging scans, and cognitive and diagnostic outcomes. The proposed T-SCCA model not only outperforms the traditional SCCA method in terms of identifying strong associations, but also discovers robust outcome-relevant imaging genetic patterns, demonstrating its promise for improving disease-related mechanistic understanding.</jats:p>","journal":"Scientific Reports","year":2017,"id":595665,"datarank":0.6038027536102726,"base_score":4.02535169073515,"endowment":4.02535169073515,"self_citation_contribution":0.6038027536102726,"citation_network_contribution":0.0,"self_endowment_contribution":0.6038027536102726,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":55,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1525392,"name":"Chanxiu Li","orcid":null,"position":1,"is_corresponding":false},{"id":291588,"name":"Lei Du","orcid":"0000-0002-6698-9814","position":2,"is_corresponding":false},{"id":53298,"name":"Xiaohui Yao","orcid":"0000-0002-8530-7989","position":3,"is_corresponding":false},{"id":829249,"name":"Jingwen Yan","orcid":"0000-0002-6153-3519","position":4,"is_corresponding":false},{"id":53156,"name":"Shannon L. Risacher","orcid":"0000-0002-3304-7943","position":5,"is_corresponding":false},{"id":27595,"name":"Andrew J. Saykin","orcid":"0000-0002-1376-8532","position":6,"is_corresponding":false},{"id":354443,"name":"Li Shen","orcid":"0000-0002-9789-9360","position":7,"is_corresponding":false},{"id":425640,"name":"Daoqiang Zhang","orcid":"0000-0002-5658-7643","position":8,"is_corresponding":false},{"id":51702,"name":"Michael W. Weiner","orcid":"0000-0002-0144-1954","position":10,"is_corresponding":false},{"id":229340,"name":"Paul Aisen","orcid":null,"position":11,"is_corresponding":false},{"id":54269,"name":"Ronald Petersen","orcid":"0009-0006-8296-6416","position":12,"is_corresponding":false},{"id":49956,"name":"Clifford R. Jack","orcid":"0000-0001-7916-622X","position":13,"is_corresponding":false},{"id":229357,"name":"Sara S. Mason","orcid":null,"position":14,"is_corresponding":false},{"id":229358,"name":"Colleen S. Albers","orcid":null,"position":15,"is_corresponding":false},{"id":66484,"name":"David Knopman","orcid":null,"position":16,"is_corresponding":false},{"id":226072,"name":"Kris Johnson","orcid":"0000-0002-3533-2043","position":17,"is_corresponding":false},{"id":51710,"name":"William Jagust","orcid":null,"position":18,"is_corresponding":false},{"id":229341,"name":"John Q. Trojanowki","orcid":null,"position":19,"is_corresponding":false},{"id":253937,"name":"Arthur W. Toga","orcid":"0000-0003-1454-8643","position":20,"is_corresponding":false},{"id":51714,"name":"Laurel Beckett","orcid":"0000-0002-2418-9843","position":21,"is_corresponding":false},{"id":584658,"name":"Robert C. Green","orcid":"0000-0003-1152-2595","position":22,"is_corresponding":false},{"id":324301,"name":"Martin R. Farlow","orcid":"0000-0001-7897-5471","position":23,"is_corresponding":false},{"id":456124,"name":"Ann Marie Hake","orcid":"0000-0001-7134-5485","position":24,"is_corresponding":false},{"id":480301,"name":"Brandy R. Matthews","orcid":null,"position":25,"is_corresponding":false},{"id":479734,"name":"Jared R. Brosch","orcid":"0000-0002-6578-0584","position":26,"is_corresponding":false},{"id":66810,"name":"Scott Herring","orcid":null,"position":27,"is_corresponding":false},{"id":636522,"name":"Cynthia Hunt","orcid":"0000-0002-6160-3361","position":28,"is_corresponding":false},{"id":27605,"name":"Leslie M. Shaw","orcid":"0000-0002-7650-1210","position":29,"is_corresponding":false},{"id":1216695,"name":"Beau Ances","orcid":null,"position":30,"is_corresponding":false},{"id":675635,"name":"John C. Morris","orcid":"0000-0002-2692-4565","position":31,"is_corresponding":false},{"id":226075,"name":"Maria Carroll","orcid":"0000-0001-6040-0565","position":32,"is_corresponding":false},{"id":401321,"name":"Mary L. Creech","orcid":null,"position":33,"is_corresponding":false},{"id":66390,"name":"Erin Franklin","orcid":null,"position":34,"is_corresponding":false},{"id":229365,"name":"Mark A. Mintun","orcid":null,"position":35,"is_corresponding":false},{"id":293703,"name":"Stacy Schneider","orcid":null,"position":36,"is_corresponding":false},{"id":400590,"name":"Angela Oliver","orcid":"0009-0004-4557-9922","position":37,"is_corresponding":false},{"id":55003,"name":"Jeffrey Kaye","orcid":"0000-0002-9971-3478","position":38,"is_corresponding":false},{"id":401320,"name":"Joseph Quinn","orcid":null,"position":39,"is_corresponding":false},{"id":66437,"name":"Lisa Silbert","orcid":null,"position":40,"is_corresponding":false},{"id":229351,"name":"Betty Lind","orcid":null,"position":41,"is_corresponding":false},{"id":229352,"name":"Raina Carter","orcid":null,"position":42,"is_corresponding":false},{"id":229353,"name":"Sara Dolen","orcid":null,"position":43,"is_corresponding":false},{"id":226069,"name":"Lon S. Schneider","orcid":"0000-0002-1875-3735","position":44,"is_corresponding":false},{"id":66454,"name":"Sonia Pawluczyk","orcid":null,"position":45,"is_corresponding":false},{"id":229354,"name":"Mauricio Beccera","orcid":null,"position":46,"is_corresponding":false},{"id":66457,"name":"Liberty Teodoro","orcid":null,"position":47,"is_corresponding":false},{"id":229355,"name":"Bryan M. Spann","orcid":null,"position":48,"is_corresponding":false},{"id":66463,"name":"James Brewer","orcid":null,"position":49,"is_corresponding":false},{"id":229356,"name":"Helen Vanderswag","orcid":null,"position":50,"is_corresponding":false},{"id":67035,"name":"Adam Fleisher","orcid":null,"position":51,"is_corresponding":false},{"id":67034,"name":"Pierre Tariot","orcid":null,"position":52,"is_corresponding":false},{"id":849587,"name":"Anna Burke","orcid":"0000-0002-0775-2518","position":53,"is_corresponding":false},{"id":66960,"name":"Nadira Trncic","orcid":null,"position":54,"is_corresponding":false},{"id":67036,"name":"Stephanie Reeder","orcid":null,"position":55,"is_corresponding":false},{"id":226070,"name":"Judith L. Heidebrink","orcid":"0000-0003-0319-9257","position":56,"is_corresponding":false},{"id":1220334,"name":"Joanne L. Lord","orcid":null,"position":57,"is_corresponding":false},{"id":229359,"name":"Rachelle S. Doody","orcid":null,"position":58,"is_corresponding":false},{"id":267240,"name":"Javier Villanueva-Meyer","orcid":"0000-0002-5910-0757","position":59,"is_corresponding":false},{"id":229361,"name":"Munir Chowdhury","orcid":null,"position":60,"is_corresponding":false},{"id":229362,"name":"Susan Rountree","orcid":null,"position":61,"is_corresponding":false},{"id":229363,"name":"Mimi Dang","orcid":null,"position":62,"is_corresponding":false},{"id":55009,"name":"Yaakov Stern","orcid":"0000-0001-7542-3241","position":63,"is_corresponding":false},{"id":108602,"name":"Lawrence S. Honig","orcid":"0000-0002-9703-2265","position":64,"is_corresponding":false},{"id":226073,"name":"Karen L. Bell","orcid":"0000-0002-0828-9465","position":65,"is_corresponding":false},{"id":325847,"name":"Daniel Marson","orcid":"0000-0002-4867-3234","position":66,"is_corresponding":false},{"id":401322,"name":"Randall Griffith","orcid":null,"position":67,"is_corresponding":false},{"id":108239,"name":"David Clark","orcid":"0000-0003-0527-8469","position":68,"is_corresponding":false},{"id":66546,"name":"David Geldmacher","orcid":null,"position":69,"is_corresponding":false},{"id":697265,"name":"John Brockington","orcid":null,"position":70,"is_corresponding":false},{"id":1525431,"name":"Erik Roberson","orcid":null,"position":71,"is_corresponding":false},{"id":688943,"name":"Marissa Natelson Love","orcid":"0000-0002-7537-3587","position":72,"is_corresponding":false},{"id":66562,"name":"Hillel Grossman","orcid":null,"position":73,"is_corresponding":false},{"id":1077384,"name":"Effie Mitsis","orcid":null,"position":74,"is_corresponding":false},{"id":284810,"name":"Raj C. Shah","orcid":"0000-0001-9706-9730","position":75,"is_corresponding":false},{"id":1525436,"name":"Leyla deToledo-Morrell","orcid":null,"position":76,"is_corresponding":false},{"id":339499,"name":"Ranjan Duara","orcid":"0000-0001-8060-6309","position":77,"is_corresponding":false},{"id":1525440,"name":"Daniel Varon","orcid":null,"position":78,"is_corresponding":false},{"id":1077391,"name":"Maria T. Greig","orcid":null,"position":79,"is_corresponding":false},{"id":1525445,"name":"Peggy Roberts","orcid":null,"position":80,"is_corresponding":false},{"id":19614,"name":"Marilyn Albert","orcid":"0000-0002-8167-8985","position":81,"is_corresponding":false},{"id":1525447,"name":"Chiadi Onyike","orcid":null,"position":82,"is_corresponding":false},{"id":1525449,"name":"Daniel D’Agostino","orcid":null,"position":83,"is_corresponding":false},{"id":1076909,"name":"Stephanie Kielb","orcid":"0000-0003-1688-2813","position":84,"is_corresponding":false},{"id":108598,"name":"James E. Galvin","orcid":"0000-0001-5678-245X","position":85,"is_corresponding":false},{"id":1525451,"name":"Brittany Cerbone","orcid":null,"position":86,"is_corresponding":false},{"id":1525453,"name":"Christina A. Michel","orcid":null,"position":87,"is_corresponding":false},{"id":1525454,"name":"Dana M. Pogorelec","orcid":null,"position":88,"is_corresponding":false},{"id":325486,"name":"Henry Rusinek","orcid":"0000-0001-6035-6314","position":89,"is_corresponding":false},{"id":431004,"name":"Mony J. de Leon","orcid":"0000-0003-4741-406X","position":90,"is_corresponding":false},{"id":729846,"name":"Lidia Glodzik","orcid":"0000-0003-4934-0949","position":91,"is_corresponding":false},{"id":842646,"name":"Susan De Santi","orcid":"0000-0002-1902-1202","position":92,"is_corresponding":false},{"id":244575,"name":"P. Murali Doraiswamy","orcid":"0000-0003-0697-3893","position":93,"is_corresponding":false},{"id":612881,"name":"Jeffrey R. Petrella","orcid":"0000-0003-2596-217X","position":94,"is_corresponding":false},{"id":1525455,"name":"Salvador Borges-Neto","orcid":null,"position":95,"is_corresponding":false},{"id":557419,"name":"Terence Z. Wong","orcid":"0000-0002-5236-9139","position":96,"is_corresponding":false},{"id":1525456,"name":"Edward Coleman","orcid":null,"position":97,"is_corresponding":false},{"id":423501,"name":"Charles D. Smith","orcid":"0000-0001-8292-9857","position":98,"is_corresponding":false},{"id":1525457,"name":"Greg Jicha","orcid":null,"position":99,"is_corresponding":false},{"id":356865,"name":"Peter Hardy","orcid":"0000-0003-0956-0138","position":100,"is_corresponding":false},{"id":1371329,"name":"Partha Sinha","orcid":null,"position":101,"is_corresponding":false},{"id":1525458,"name":"Elizabeth Oates","orcid":null,"position":102,"is_corresponding":false},{"id":1525459,"name":"Gary Conrad","orcid":null,"position":103,"is_corresponding":false},{"id":231709,"name":"Anton P. Porsteinsson","orcid":"0000-0002-0166-1738","position":104,"is_corresponding":false},{"id":1525460,"name":"Bonnie S. Goldstein","orcid":null,"position":105,"is_corresponding":false},{"id":1525461,"name":"Kim Martin","orcid":null,"position":106,"is_corresponding":false},{"id":1525462,"name":"Kelly M. Makino","orcid":null,"position":107,"is_corresponding":false},{"id":1525463,"name":"M. Saleem Ismail","orcid":null,"position":108,"is_corresponding":false},{"id":67976,"name":"Connie Brand","orcid":null,"position":109,"is_corresponding":false},{"id":1525464,"name":"Ruth A. Mulnard","orcid":null,"position":110,"is_corresponding":false},{"id":66689,"name":"Gaby Thai","orcid":null,"position":111,"is_corresponding":false},{"id":1525465,"name":"Catherine Mc-Adams-Ortiz","orcid":null,"position":112,"is_corresponding":false},{"id":525677,"name":"Kyle Womack","orcid":"0000-0002-6060-9075","position":113,"is_corresponding":false},{"id":66711,"name":"Dana Mathews","orcid":null,"position":114,"is_corresponding":false},{"id":1525466,"name":"Mary Quiceno","orcid":null,"position":115,"is_corresponding":false},{"id":68010,"name":"Allan I. Levey","orcid":"0000-0002-3153-502X","position":116,"is_corresponding":false},{"id":107095,"name":"James J. Lah","orcid":"0000-0002-8810-620X","position":117,"is_corresponding":false},{"id":1525467,"name":"Janet S. Cellar","orcid":null,"position":118,"is_corresponding":false},{"id":68016,"name":"Jeffrey M. Burns","orcid":"0000-0001-7609-8954","position":119,"is_corresponding":false},{"id":107455,"name":"Russell H. Swerdlow","orcid":"0000-0003-2948-7230","position":120,"is_corresponding":false},{"id":294103,"name":"William M. Brooks","orcid":"0000-0001-6227-7636","position":121,"is_corresponding":false},{"id":178507,"name":"Liana Apostolova","orcid":null,"position":122,"is_corresponding":false},{"id":1525468,"name":"Kathleen Tingus","orcid":null,"position":123,"is_corresponding":false},{"id":446598,"name":"Ellen Woo","orcid":null,"position":124,"is_corresponding":false},{"id":1525469,"name":"Daniel H. S. Silverman","orcid":null,"position":125,"is_corresponding":false},{"id":1525470,"name":"Po H. Lu","orcid":null,"position":126,"is_corresponding":false},{"id":1525471,"name":"George Bartzokis","orcid":null,"position":127,"is_corresponding":false},{"id":914816,"name":"Neill R. Graff-Radford","orcid":null,"position":128,"is_corresponding":false},{"id":480299,"name":"Francine Parfitt","orcid":null,"position":129,"is_corresponding":false},{"id":1525472,"name":"Tracy Kendall","orcid":null,"position":130,"is_corresponding":false},{"id":418491,"name":"Heather Johnson","orcid":"0000-0002-1059-1954","position":131,"is_corresponding":false},{"id":235262,"name":"Christopher H. van Dyck","orcid":"0000-0003-1779-097X","position":132,"is_corresponding":false},{"id":235261,"name":"Richard E. Carson","orcid":"0000-0002-9338-7966","position":133,"is_corresponding":false},{"id":1525473,"name":"Martha G. MacAvoy","orcid":null,"position":134,"is_corresponding":false},{"id":238637,"name":"Pradeep Varma","orcid":null,"position":135,"is_corresponding":false},{"id":2717,"name":"Howard Chertkow","orcid":"0000-0003-3749-8132","position":136,"is_corresponding":false},{"id":66850,"name":"Howard Bergman","orcid":null,"position":137,"is_corresponding":false},{"id":66851,"name":"Chris Hosein","orcid":null,"position":138,"is_corresponding":false},{"id":66852,"name":"Sandra Black","orcid":null,"position":139,"is_corresponding":false},{"id":688951,"name":"Bojana Stefanovic","orcid":"0000-0002-8439-7601","position":140,"is_corresponding":false},{"id":1525489,"name":"Curtis Caldwell","orcid":null,"position":141,"is_corresponding":false},{"id":1525492,"name":"Ging-Yuek Robin Hsiung","orcid":null,"position":142,"is_corresponding":false},{"id":58516,"name":"Howard Feldman","orcid":"0000-0002-9258-4538","position":143,"is_corresponding":false},{"id":1525497,"name":"Benita Mudge","orcid":null,"position":144,"is_corresponding":false},{"id":66875,"name":"Michele Assaly","orcid":null,"position":145,"is_corresponding":false},{"id":635052,"name":"Elizabeth Finger","orcid":"0000-0003-4461-7427","position":146,"is_corresponding":false},{"id":1525501,"name":"Stephen Pasternack","orcid":null,"position":147,"is_corresponding":false},{"id":1525503,"name":"Irina Rachisky","orcid":null,"position":148,"is_corresponding":false},{"id":66880,"name":"Dick Trost","orcid":null,"position":149,"is_corresponding":false},{"id":66878,"name":"Andrew Kertesz","orcid":null,"position":150,"is_corresponding":false},{"id":66882,"name":"Charles Bernick","orcid":"0000-0003-4040-3587","position":151,"is_corresponding":false},{"id":66883,"name":"Donna Munic","orcid":null,"position":152,"is_corresponding":false},{"id":415185,"name":"Marek-Marsel Mesulam","orcid":null,"position":153,"is_corresponding":false},{"id":604208,"name":"Kristine Lipowski","orcid":null,"position":154,"is_corresponding":false},{"id":49966,"name":"Sandra Weintraub","orcid":null,"position":155,"is_corresponding":false},{"id":351167,"name":"Borna Bonakdarpour","orcid":"0000-0003-0028-0535","position":156,"is_corresponding":false},{"id":253923,"name":"Diana Kerwin","orcid":"0009-0003-0639-5808","position":157,"is_corresponding":false},{"id":67101,"name":"Chuang-Kuo Wu","orcid":null,"position":158,"is_corresponding":false},{"id":1525508,"name":"Nancy Johnson","orcid":null,"position":159,"is_corresponding":false},{"id":66895,"name":"Carl Sadowsky","orcid":null,"position":160,"is_corresponding":false},{"id":66897,"name":"Teresa Villena","orcid":null,"position":161,"is_corresponding":false},{"id":269676,"name":"Raymond Scott Turner","orcid":"0000-0001-7534-2935","position":162,"is_corresponding":false},{"id":66905,"name":"Kathleen Johnson","orcid":null,"position":163,"is_corresponding":false},{"id":66898,"name":"Brigid Reynolds","orcid":null,"position":164,"is_corresponding":false},{"id":55000,"name":"Reisa A. Sperling","orcid":"0000-0003-1535-6133","position":165,"is_corresponding":false},{"id":1229162,"name":"Keith A. Johnson","orcid":"0000-0002-4685-5173","position":166,"is_corresponding":false},{"id":66914,"name":"Gad Marshall","orcid":null,"position":167,"is_corresponding":false},{"id":1525510,"name":"Jerome Yesavage","orcid":null,"position":168,"is_corresponding":false},{"id":585985,"name":"Joy L. Taylor","orcid":"0000-0002-5776-3995","position":169,"is_corresponding":false},{"id":492783,"name":"Barton Lane","orcid":"0000-0002-7088-1910","position":170,"is_corresponding":false},{"id":871026,"name":"Allyson Rosen","orcid":"0000-0003-2222-7882","position":171,"is_corresponding":false},{"id":871815,"name":"Jared Tinklenberg","orcid":null,"position":172,"is_corresponding":false},{"id":459229,"name":"Marwan N. Sabbagh","orcid":"0000-0001-8139-3309","position":173,"is_corresponding":false},{"id":459231,"name":"Christine M. Belden","orcid":"0000-0001-9833-7100","position":174,"is_corresponding":false},{"id":1525517,"name":"Sandra A. Jacobson","orcid":null,"position":175,"is_corresponding":false},{"id":1525518,"name":"Sherye A. Sirrel","orcid":null,"position":176,"is_corresponding":false},{"id":1204753,"name":"Neil Kowall","orcid":null,"position":177,"is_corresponding":false},{"id":19615,"name":"Ronald Killiany","orcid":"0000-0003-4740-2181","position":178,"is_corresponding":false},{"id":67995,"name":"Andrew E. Budson","orcid":"0000-0002-2913-0015","position":179,"is_corresponding":false},{"id":628605,"name":"Alexander Norbash","orcid":"0000-0003-2986-2563","position":180,"is_corresponding":false},{"id":1525519,"name":"Patricia Lynn Johnson","orcid":null,"position":181,"is_corresponding":false},{"id":480523,"name":"Thomas O. Obisesan","orcid":"0000-0002-0291-512X","position":182,"is_corresponding":false},{"id":1525520,"name":"Saba Wolday","orcid":null,"position":183,"is_corresponding":false},{"id":948804,"name":"Joanne Allard","orcid":null,"position":184,"is_corresponding":false},{"id":1396150,"name":"Alan Lerner","orcid":null,"position":185,"is_corresponding":false},{"id":67007,"name":"Paula Ogrocki","orcid":null,"position":186,"is_corresponding":false},{"id":67977,"name":"Curtis Tatsuoka","orcid":"0000-0001-9991-4440","position":187,"is_corresponding":false},{"id":67006,"name":"Parianne Fatica","orcid":null,"position":188,"is_corresponding":false},{"id":66379,"name":"Evan Fletcher","orcid":null,"position":189,"is_corresponding":false},{"id":277081,"name":"Pauline Maillard","orcid":"0000-0003-3516-6345","position":190,"is_corresponding":false},{"id":303071,"name":"John Olichney","orcid":null,"position":191,"is_corresponding":false},{"id":277082,"name":"Charles DeCarli","orcid":"0000-0003-1914-2693","position":192,"is_corresponding":false},{"id":277080,"name":"Owen Carmichael","orcid":"0000-0002-0576-0047","position":193,"is_corresponding":false},{"id":1525528,"name":"Smita Kittur","orcid":null,"position":194,"is_corresponding":false},{"id":67027,"name":"Michael Borrie","orcid":null,"position":195,"is_corresponding":false},{"id":1525530,"name":"T.-Y. Lee","orcid":null,"position":196,"is_corresponding":false},{"id":67029,"name":"Rob Bartha","orcid":null,"position":197,"is_corresponding":false},{"id":67030,"name":"Sterling Johnson","orcid":null,"position":198,"is_corresponding":false},{"id":1254558,"name":"Sanjay Asthana","orcid":"0000-0002-3298-6324","position":199,"is_corresponding":false},{"id":67032,"name":"Cynthia M. Carlsson","orcid":null,"position":200,"is_corresponding":false},{"id":226064,"name":"Steven G. Potkin","orcid":"0000-0003-1028-1013","position":201,"is_corresponding":false},{"id":236942,"name":"Adrian Preda","orcid":"0000-0003-3373-2438","position":202,"is_corresponding":false},{"id":548371,"name":"Dana Nguyen","orcid":"0000-0003-3506-9350","position":203,"is_corresponding":false},{"id":67059,"name":"Vernice Bates","orcid":null,"position":204,"is_corresponding":false},{"id":67037,"name":"Horacio Capote","orcid":null,"position":205,"is_corresponding":false},{"id":67052,"name":"Michelle Rainka","orcid":null,"position":206,"is_corresponding":false},{"id":67062,"name":"Douglas W. Scharre","orcid":null,"position":207,"is_corresponding":false},{"id":66500,"name":"Maria Kataki","orcid":null,"position":208,"is_corresponding":false},{"id":1525532,"name":"Anahita Adeli","orcid":null,"position":209,"is_corresponding":false},{"id":268961,"name":"Earl A. Zimmerman","orcid":null,"position":210,"is_corresponding":false},{"id":67066,"name":"Dzintra Celmins","orcid":null,"position":211,"is_corresponding":false},{"id":1525533,"name":"Alice D. Brown","orcid":null,"position":212,"is_corresponding":false},{"id":67074,"name":"Godfrey D. Pearlson","orcid":null,"position":213,"is_corresponding":false},{"id":67075,"name":"Karen Blank","orcid":null,"position":214,"is_corresponding":false},{"id":804402,"name":"Karen Anderson","orcid":"0000-0002-1176-6605","position":215,"is_corresponding":false},{"id":450265,"name":"Laura A. Flashman","orcid":null,"position":216,"is_corresponding":false},{"id":1525534,"name":"Marc Seltzer","orcid":null,"position":217,"is_corresponding":false},{"id":1525535,"name":"Mary L. Hynes","orcid":null,"position":218,"is_corresponding":false},{"id":67077,"name":"Robert B. Santulli","orcid":null,"position":219,"is_corresponding":false},{"id":295978,"name":"Kaycee M. Sink","orcid":"0000-0001-9608-3856","position":220,"is_corresponding":false},{"id":1525536,"name":"Leslie Gordineer","orcid":null,"position":221,"is_corresponding":false},{"id":295973,"name":"Jeff D. Williamson","orcid":"0000-0002-0185-5823","position":222,"is_corresponding":false},{"id":1525537,"name":"Pradeep Garg","orcid":null,"position":223,"is_corresponding":false},{"id":1525538,"name":"Franklin Watkins","orcid":null,"position":224,"is_corresponding":false},{"id":670382,"name":"Brian R. Ott","orcid":"0000-0002-4899-7116","position":225,"is_corresponding":false},{"id":382057,"name":"Henry Querfurth","orcid":null,"position":226,"is_corresponding":false},{"id":1124409,"name":"Geoffrey Tremont","orcid":"0000-0002-1506-0722","position":227,"is_corresponding":false},{"id":67115,"name":"Stephen Salloway","orcid":null,"position":228,"is_corresponding":false},{"id":67116,"name":"Paul Malloy","orcid":null,"position":229,"is_corresponding":false},{"id":430526,"name":"Stephen Correia","orcid":"0000-0003-3416-3660","position":230,"is_corresponding":false},{"id":67119,"name":"Howard J. Rosen","orcid":null,"position":231,"is_corresponding":false},{"id":58513,"name":"Bruce L. Miller","orcid":"0000-0002-2152-4220","position":232,"is_corresponding":false},{"id":1454056,"name":"David Perry","orcid":null,"position":233,"is_corresponding":false},{"id":67157,"name":"Jacobo Mintzer","orcid":null,"position":234,"is_corresponding":false},{"id":67159,"name":"Kenneth Spicer","orcid":null,"position":235,"is_corresponding":false},{"id":1525539,"name":"David Bachman","orcid":null,"position":236,"is_corresponding":false},{"id":886917,"name":"Nunzio Pomara","orcid":"0000-0002-8075-4253","position":237,"is_corresponding":false},{"id":67141,"name":"Raymundo Hernando","orcid":null,"position":238,"is_corresponding":false},{"id":68059,"name":"Antero Sarrael","orcid":null,"position":239,"is_corresponding":false},{"id":291654,"name":"Norman Relkin","orcid":"0000-0003-2495-950X","position":240,"is_corresponding":false},{"id":1525540,"name":"Gloria Chaing","orcid":null,"position":241,"is_corresponding":false},{"id":380817,"name":"Michael Lin","orcid":"0000-0002-8275-7140","position":242,"is_corresponding":false},{"id":746903,"name":"Lisa Ravdin","orcid":"0000-0003-3959-9682","position":243,"is_corresponding":false},{"id":916385,"name":"Amanda Smith","orcid":"0000-0002-5698-872X","position":244,"is_corresponding":false},{"id":1077392,"name":"Balebail Ashok Raj","orcid":null,"position":245,"is_corresponding":false},{"id":1077393,"name":"Kristin Fargher","orcid":null,"position":246,"is_corresponding":false},{"id":1525391,"name":"Xiaoke Hao","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mining Outcome-relevant Brain Imaging Genetic Associations via Three-way Sparse Canonical Correlation Analysis in Alzheimer’s Disease","abstract":"<jats:title>Abstract</jats:title><jats:p>Neuroimaging genetics is an emerging field that aims to identify the associations between genetic variants (e.g., single nucleotide polymorphisms (SNPs)) and quantitative traits (QTs) such as brain imaging phenotypes. In recent studies, in order to detect complex multi-SNP-multi-QT associations, bi-multivariate techniques such as various structured sparse canonical correlation analysis (SCCA) algorithms have been proposed and used in imaging genetics studies. However, associations between genetic markers and imaging QTs identified by existing bi-multivariate methods may not be all disease specific. To bridge this gap, we propose an analytical framework, based on three-way sparse canonical correlation analysis (T-SCCA), to explore the intrinsic associations among genetic markers, imaging QTs, and clinical scores of interest. We perform an empirical study using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort to discover the relationships among SNPs from AD risk gene<jats:italic>APOE</jats:italic>, imaging QTs extracted from structural magnetic resonance imaging scans, and cognitive and diagnostic outcomes. The proposed T-SCCA model not only outperforms the traditional SCCA method in terms of identifying strong associations, but also discovers robust outcome-relevant imaging genetic patterns, demonstrating its promise for improving disease-related mechanistic understanding.</jats:p>","is_dataset_classified":null,"base_score":4.02535169073515,"endowment":4.02535169073515,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28291242","pmcid":"PMC5349597","openalex_id":"https://openalex.org/W2607528709","authors":[],"funders":[{"funder_name":"NLM NIH HHS","grant_id":"R01 LM011360","title":null},{"funder_name":"NIA NIH HHS","grant_id":"U01 AG024904","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR001108","title":null},{"funder_name":"NIA NIH HHS","grant_id":"P30 AG010129","title":null},{"funder_name":"NIBIB NIH HHS","grant_id":"P41 EB015922","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG046171","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG042437","title":null},{"funder_name":"NIA NIH HHS","grant_id":"RC2 AG036535","title":null},{"funder_name":"NIA NIH HHS","grant_id":"P30 AG010133","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG019771","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"unidentified","title":"unidentified"},{"funder_name":"National Institutes of Health","grant_id":"2R01AG019771-06","title":"Memory Circuitry in MCI and Early Alzheimers Disease"},{"funder_name":"National Institutes of Health","grant_id":"1U01AG024904-01","title":"Alzheimers Disease Neuroimaging Initiative"},{"funder_name":"National Institutes of Health","grant_id":"3UL1TR001108-02S1","title":"Indiana Clinical and Translational Sciences Institute"},{"funder_name":"National Institutes of Health","grant_id":"5R01AG046171-03","title":"Metabolic Networks and Pathways in Alzheimer's Disease"},{"funder_name":"National Science Foundation","grant_id":"1117335","title":"III: Small: Collaborative Research: A Large-Scale Data Mining Framework for Genome-Wide Mapping of Multi-Modal Phenotypic Biomarkers and Outcome Prediction"},{"funder_name":"National Institutes of Health","grant_id":"5P30AG010133-08","title":"CORE-- EDUCATION AND INFORMATION TRANSFER"},{"funder_name":"National Institutes of Health","grant_id":"1RC2AG036535-01","title":"Amyloid Imaging, VMCI, and Analysis for ADNI"},{"funder_name":"National Institutes of Health","grant_id":"5R01LM011360-03","title":"Bioinformatics Strategies for Multidimensional Brain Imaging Genetics"}],"total_grants":19,"fwci":2.0473,"citation_percentile":0.86645107,"influential_citations":0,"citation_trend":[{"year":2017,"count":1},{"year":2018,"count":4},{"year":2019,"count":4},{"year":2020,"count":9},{"year":2021,"count":9},{"year":2022,"count":15},{"year":2023,"count":6},{"year":2024,"count":4},{"year":2025,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/srep44272.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/srep44272.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/srep44272","host_type":"publisher"},{"url":"https://doi.org/10.1038/srep44272","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28291242","host_type":"repository"},{"url":"http://nrs.harvard.edu/urn-3:HUL.InstRepos:32071994","host_type":"repository"},{"url":"https://escholarship.org/uc/item/15h9166m","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5349597","host_type":"repository"},{"url":"https://hdl.handle.net/1805/13557","host_type":"repository"},{"url":"http://hdl.handle.net/1805/13557","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5349597","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5349597?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1038/srep44272","host_type":""},{"url":"https://dx.doi.org/10.1038/srep44272","host_type":""},{"url":"https://escholarship.org/content/qt15h9166m/qt15h9166m.pdf","host_type":""},{"url":"https://doi.org/https://doi.org/10.1038/srep44272","host_type":""}],"fields_of_study":["Functional Brain Connectivity Studies","Dementia and Cognitive Impairment Research","Genetic Associations and Epidemiology","0301 basic medicine","0302 clinical medicine","03 medical and health sciences","Algorithms","Alzheimer Disease","Apolipoproteins E","Brain","Cognitive Dysfunction","Cohort Studies","Data Mining","Datasets as Topic","Gene Expression","Genetic Association Studies","Genetic Predisposition to Disease","Humans","Magnetic Resonance Imaging","Multivariate Analysis","Neuroimaging","Phenotype","Polymorphism, Single Nucleotide","Severity of Illness Index"],"mesh_terms":["Algorithms","Alzheimer Disease","Apolipoproteins E","Brain","Humans","Magnetic Resonance Imaging","Phenotype","Severity of Illness Index","Cohort Studies","Gene Expression","Multivariate Analysis","Genetic Predisposition to Disease","Polymorphism, Single Nucleotide","Genetic Association Studies","Data Mining","Neuroimaging","Cognitive Dysfunction","Datasets as Topic"],"keywords":["Alzheimer's Disease Neuroimaging Initiative","Imaging genetics","Neuroimaging","Canonical correlation","Multivariate statistics","Correlation","Single-nucleotide polymorphism","Computational biology","SNP","Disease","Multivariate analysis","Magnetic resonance imaging","Biology","Bioinformatics","Computer science","Artificial intelligence","Alzheimer's disease","Machine learning","Genetics","Neuroscience","Medicine","Gene","Pathology","Genotype","Mathematics","Genetic variants","Aging","Genetics studies","Datasets as Topic","Gene Expression","Neurodegenerative","Severity of Illness Index","Cohort Studies","2.1 Biological and endogenous factors","Data Mining","Brain imaging phenotypes","Brain","Single Nucleotide","Biological Sciences","Phenotype","Neurological","Biomedical Imaging","Algorithms","610","Polymorphism, Single Nucleotide","Article","Apolipoproteins E","Alzheimer Disease","616","Acquired Cognitive Impairment","Humans","Cognitive Dysfunction","Genetic Predisposition to Disease","Polymorphism","Genetic Association Studies","Prevention","Human Genome","Neurosciences","Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)","Neuroimaging genetics","Single nucleotide polymorphisms","Alzheimer’s Disease Neuroimaging Initiative","Genetic patterns","Brain Disorders","4.1 Discovery and preclinical testing of markers and technologies","Genetic markers","Dementia"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"refsnp"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T17:46:04.430124Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}