Mining Outcome-relevant Brain Imaging Genetic Associations via Three-way Sparse Canonical Correlation Analysis in Alzheimer’s Disease

• DOI: 10.1038/srep44272
• Publication Date: 2017-03-14T14:26:56Z
• Authors: Xiaoke Hao; Chanxiu Li; Lei Du; Xiaohui Yao; Jingwen Yan; Shannon L. Risacher; Andrew J. Saykin; Li Shen; Daoqiang Zhang; ; Michael W. Weiner; Paul Aisen; Ronald Petersen; Clifford R. Jack; Sara S. Mason; Colleen S. Albers; David Knopman; Kris Johnson; William Jagust; John Q. Trojanowki; Arthur W. Toga; Laurel Beckett; Robert C. Green; Martin R. Farlow; Ann Marie Hake; Brandy R. Matthews; Jared R. Brosch; Scott Herring; Cynthia Hunt; Leslie M. Shaw; Beau Ances; John C. Morris; Maria Carroll; Mary L. Creech; Erin Franklin; Mark A. Mintun; Stacy Schneider; Angela Oliver; Jeffrey Kaye; Joseph Quinn; Lisa Silbert; Betty Lind; Raina Carter; Sara Dolen; Lon S. Schneider; Sonia Pawluczyk; Mauricio Beccera; Liberty Teodoro; Bryan M. Spann; James Brewer; Helen Vanderswag; Adam Fleisher; Pierre Tariot; Anna Burke; Nadira Trncic; Stephanie Reeder; Judith L. Heidebrink; Joanne L. Lord; Rachelle S. Doody; Javier Villanueva...; Munir Chowdhury; Susan Rountree; Mimi Dang; Yaakov Stern; Lawrence S. Honig; Karen L. Bell; Daniel Marson; Randall Griffith; David Clark; David Geldmacher; John Brockington; Erik Roberson; Marissa Natelson ...; Hillel Grossman; Effie Mitsis; Raj C. Shah; Leyla deToledo-Mo...; Ranjan Duara; Daniel Varon; Maria T. Greig; Peggy Roberts; Marilyn Albert; Chiadi Onyike; Daniel D’Agostino; Stephanie Kielb; James E. Galvin; Brittany Cerbone; Christina A. Michel; Dana M. Pogorelec; Henry Rusinek; Mony J. de Leon; Lidia Glodzik; Susan De Santi; P. Murali Doraiswamy; Jeffrey R. Petrella; Salvador Borges-Neto; Terence Z. Wong; Edward Coleman; Charles D. Smith; Greg Jicha; Peter Hardy; Partha Sinha; Elizabeth Oates; Gary Conrad; Anton P. Porstein...; Bonnie S. Goldstein; Kim Martin; Kelly M. Makino; M. Saleem Ismail; Connie Brand; Ruth A. Mulnard; Gaby Thai; Catherine Mc-Adam...; Kyle Womack; Dana Mathews; Mary Quiceno; Allan I. Levey; James J. Lah; Janet S. Cellar; Jeffrey M. Burns; Russell H. Swerdlow; William M. Brooks; Liana Apostolova; Kathleen Tingus; Ellen Woo; Daniel H. S. Silv...; Po H. Lu; George Bartzokis; Neill R. Graff-Ra...; Francine Parfitt; Tracy Kendall; Heather Johnson; Christopher H. va...; Richard E. Carson; Martha G. MacAvoy; Pradeep Varma; Howard Chertkow; Howard Bergman; Chris Hosein; Sandra Black; Bojana Stefanovic; Curtis Caldwell; Ging-Yuek Robin H...; Howard Feldman; Benita Mudge; Michele Assaly; Elizabeth Finger; Stephen Pasternack; Irina Rachisky; Dick Trost; Andrew Kertesz; Charles Bernick; Donna Munic; Marek-Marsel Mesulam; Kristine Lipowski; Sandra Weintraub; Borna Bonakdarpour; Diana Kerwin; Chuang-Kuo Wu; Nancy Johnson; Carl Sadowsky; Teresa Villena; Raymond Scott Turner; Kathleen Johnson; Brigid Reynolds; Reisa A. Sperling; Keith A. Johnson; Gad Marshall; Jerome Yesavage; Joy L. Taylor; Barton Lane; Allyson Rosen; Jared Tinklenberg; Marwan N. Sabbagh; Christine M. Belden; Sandra A. Jacobson; Sherye A. Sirrel; Neil Kowall; Ronald Killiany; Andrew E. Budson; Alexander Norbash; Patricia Lynn Joh...; Thomas O. Obisesan; Saba Wolday; Joanne Allard; Alan Lerner; Paula Ogrocki; Curtis Tatsuoka; Parianne Fatica; Evan Fletcher; Pauline Maillard; John Olichney; Charles DeCarli; Owen Carmichael; Smita Kittur; Michael Borrie; T.-Y. Lee; Rob Bartha; Sterling Johnson; Sanjay Asthana; Cynthia M. Carlsson; Steven G. Potkin; Adrian Preda; Dana Nguyen; Vernice Bates; Horacio Capote; Michelle Rainka; Douglas W. Scharre; Maria Kataki; Anahita Adeli; Earl A. Zimmerman; Dzintra Celmins; Alice D. Brown; Godfrey D. Pearlson; Karen Blank; Karen Anderson; Laura A. Flashman; Marc Seltzer; Mary L. Hynes; Robert B. Santulli; Kaycee M. Sink; Leslie Gordineer; Jeff D. Williamson; Pradeep Garg; Franklin Watkins; Brian R. Ott; Henry Querfurth; Geoffrey Tremont; Stephen Salloway; Paul Malloy; Stephen Correia; Howard J. Rosen; Bruce L. Miller; David Perry; Jacobo Mintzer; Kenneth Spicer; David Bachman; Nunzio Pomara; Raymundo Hernando; Antero Sarrael; Norman Relkin; Gloria Chaing; Michael Lin; Lisa Ravdin; Amanda Smith; Balebail Ashok Raj; Kristin Fargher
• Keywords: Genetic variants; Aging; Genetics studies; Datasets as Topic; Gene Expression; Neurodegenerative; Alzheimer's Disease; Severity of Illness Index; Cohort Studies; 0302 clinical medicine; 2.1 Biological and endogenous factors; Data Mining; Brain imaging phenotypes; Brain; Single Nucleotide; Biological Sciences; Magnetic Resonance Imaging; 3. Good health; Phenotype; Neurological; Biomedical Imaging; Algorithms; 610; Neuroimaging; Polymorphism, Single Nucleotide; Article; 03 medical and health sciences; Apolipoproteins E; Alzheimer Disease; 616; Genetics; 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; Multivariate Analysis; Genetic markers; Dementia

AbstractNeuroimaging 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 APOE, 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.