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Many studies have shown that the structure, function, and abnormality (e.g., those related to Alzheimer\u2019s disease) of the brain are heritable. However, which genetic variations contribute to these phenotypic changes is not completely clear. Advances in neuroimaging and genetics have led us to obtain detailed brain anatomy and genome-wide information. These data offer us new opportunities to identify genetic variations such as single nucleotide polymorphisms (SNPs) that affect brain structure. In this paper, we perform a genome-wide variant-based study, and aim to identify top SNPs or SNP sets which have genetic effects with the largest neuroanotomic coverage at both voxel and region-of-interest (ROI) levels. Based on the voxelwise genome-wide association study (GWAS) results, we used the exhaustive search to find the top SNPs or SNP sets that have the largest voxel-based or ROI-based neuroanatomic coverage. For SNP sets with &gt;2 SNPs, we proposed an efficient genetic algorithm to identify top SNP sets that can cover all ROIs or a specific ROI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified an ensemble of top SNPs, SNP-pairs and SNP-sets, whose effects have the largest neuroanatomic coverage. Experimental results on real imaging genetics data show that the proposed genetic algorithm is superior to the exhaustive search in terms of computational time for identifying top SNP-sets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We proposed and applied an informatics strategy to identify top SNPs, SNP-pairs and SNP-sets that have genetic effects with the largest neuroanatomic coverage. 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Ethics approval was obtained from the institutional review boards of each institution involved: Oregon Health and Science University; University of Southern California; University of California-San Diego; University of Michigan; Mayo Clinic, Rochester; Baylor College of Medicine; Columbia University Medical Center; Washington University, St. Louis; University of Alabama at Birmingham; Mount Sinai School of Medicine; Rush University Medical Center; Wien Center; Johns Hopkins University; New York University; Duke University Medical Center; University of Pennsylvania; University of Kentucky; University of Pittsburgh; University of Rochester Medical Center; University of California, Irvine; University of Texas Southwestern Medical School; Emory University; University of Kansas, Medical Center; University of California, Los Angeles; Mayo Clinic, Jacksonville; Indiana University; Yale University School of Medicine; McGill University, Montreal-Jewish General Hospital; Sunnybrook Health Sciences, Ontario; U.B.C.Clinic for AD & Related Disorders; Cognitive Neurology-St. Joseph\u2019s, Ontario; Cleveland Clinic Lou Ruvo Center for Brain Health; Northwestern University; Premiere Research Inst (Palm Beach Neurology); Georgetown University Medical Center; Brigham and Women\u2019s Hospital; Stanford University; Banner Sun Health Research Institute; Boston University; Howard University; Case Western Reserve University; University of California, Davis-Sacramento; Neurological Care of CNY; Parkwood Hospital; University of Wisconsin; University of California, Irvine-BIC; Banner Alzheimer\u2019s Institute; Dent Neurologic Institute; Ohio State University; Albany Medical College; Hartford Hospital, Olin Neuropsychiatry Research Center; Dartmouth-Hitchcock Medical Center; Wake Forest University Health Sciences; Rhode Island Hospital; Butler Hospital; UC San Francisco; Medical University South Carolina; St. Joseph\u2019s Health Care Nathan Kline Institute; University of Iowa College of Medicine; Cornell University; and University of South Florida: USF Health Byrd Alzheimer\u2019s Institute.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors have no actual or potential conflicts of interest including any financial, personal, or other relationships with other people or organizations that could inappropriately influence (bias) our work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"223"}}