{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T03:11:36Z","timestamp":1767928296853,"version":"3.49.0"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,11,18]],"date-time":"2016-11-18T00:00:00Z","timestamp":1479427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01 DA016750"],"award-info":[{"award-number":["R01 DA016750"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["T32 MH 14235"],"award-info":[{"award-number":["T32 MH 14235"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RC2DA029475"],"award-info":[{"award-number":["RC2DA029475"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RC2MH089983"],"award-info":[{"award-number":["RC2MH089983"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RC2MH089924"],"award-info":[{"award-number":["RC2MH089924"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Specific learning disorders (SLD) are an archetypal example of how clinical neuropsychological (NP) traits can differ from underlying genetic and neurobiological risk factors. Disparate environmental influences and pathologies impact learning performance assessed through cognitive examinations and clinical evaluations, the primary diagnostic tools for SLD. We propose a neurobiological risk for SLD with neuroimaging biomarkers, which is integrated into a genome\u2010wide association study (GWAS) of learning performance in a cohort of 479 European individuals between 8 and 21 years of age. We first identified six regions of interest (ROIs) in temporal and anterior cingulate regions where the group diagnosed with learning disability has the least overall variation, relative to the other group, in thickness, area, and volume measurements. Although we used the three imaging measures, the thickness was the leading contributor. Hence, we calculated the Euclidean distances between any two individuals based on their thickness measures in the six ROIs. Then, we defined the relative similarity of one individual according to the averaged ranking of pairwise distances from the individuals to those in the SLD group. The inverse of this relative similarity is called the neurobiological risk for the individual. Single nucleotide polymorphisms in the <jats:italic>AGBL1<\/jats:italic> gene on chromosome 15 had a significant association with learning performance at a genome\u2010wide level. This finding was supported in an independent cohort of 2,327 individuals of the same demographic profile. Our statistical approach for integrating genetic and neuroimaging biomarkers can be extended into studying the biological basis of other NP traits.<\/jats:p>","DOI":"10.1002\/gepi.22025","type":"journal-article","created":{"date-parts":[[2016,11,18]],"date-time":"2016-11-18T09:37:11Z","timestamp":1479461831000},"page":"4-17","source":"Crossref","is-referenced-by-count":13,"title":["A method for integrating neuroimaging into genetic models of learning performance"],"prefix":"10.1002","volume":"41","author":[{"given":"Chintan M.","family":"Mehta","sequence":"first","affiliation":[{"name":"Department of Biostatistics Yale University  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey R.","family":"Gruen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Genetics Yale University  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Yale University  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000473"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1037\/neu0000001"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-2089L"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013353613591"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.clinpsy.1.102803.143959"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-005-0084-6"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/brln.1997.1844"},{"key":"e_1_2_6_10_1","unstructured":"Castle M.(2002).Learning disabilities and early intervention strategies: How to reform the special education referral and identification process. Subcommittee on Education Reform House of Representatives 107th Congress (p. 1)."},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400266101"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2005.01.016"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291712002656"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2809"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addbeh.2014.01.004"},{"key":"e_1_2_6_16_1","volume-title":"Learning disabilities: From identification to intervention","author":"Fletcher J. M.","year":"2007"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291708004558"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.08.022"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0123886"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0808700"},{"key":"e_1_2_6_21_1","doi-asserted-by":"crossref","unstructured":"Harlaar N. Spinath F. M. Dale P. S. &Plomin R.(2005).Genetic influences on early word recognition abilities and disabilities: A study of 7\u2010year\u2010old twins 46(4) 373\u2013384. Retrieved fromhttp:\/\/doi.org\/10.1111\/j.1469-7610.2004.00358.x","DOI":"10.1111\/j.1469-7610.2004.00358.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20080"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.94"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab2358"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.04.057"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.63.3.250"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0b013e328350360e"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11065-009-9107-0"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2711"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/070674370705201104"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2006.04.012"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.07.026"},{"key":"e_1_2_6_33_1","first-page":"29","article-title":"A review of multivariate analyses in imaging genetics","volume":"8","author":"Liu J.","year":"2014","journal-title":"Frontiers in Neuroinformatics"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.06.009"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.22.1.105"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.10.063"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1993"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3983"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2006.07.005"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17671"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1037\/a0022569"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13595"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1516\/ATTU-2M15-HX4F-5R2V"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.10.014"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.07.064"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.07.007"},{"key":"e_1_2_6_48_1","article-title":"missForest: Nonparametric missing value imputation using random forest","author":"Stekhoven D. J.","year":"2013","journal-title":"R Package Version 1.4"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr597"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2008.25"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.11.029"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2006.07.009"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182872ded"},{"key":"e_1_2_6_54_1","article-title":"Wide range achievement test (WRAT4)","author":"Wilkinson G.","year":"2006","journal-title":"Psychological Assessment Resources, Lutz"}],"container-title":["Genetic Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgepi.22025","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gepi.22025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T19:39:19Z","timestamp":1696361959000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gepi.22025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,18]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1002\/gepi.22025"],"URL":"https:\/\/doi.org\/10.1002\/gepi.22025","archive":["Portico"],"relation":{},"ISSN":["0741-0395","1098-2272"],"issn-type":[{"value":"0741-0395","type":"print"},{"value":"1098-2272","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,18]]}}}