{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T19:46:37Z","timestamp":1769111197941,"version":"3.49.0"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,9,10]],"date-time":"2015-09-10T00:00:00Z","timestamp":1441843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["IIRG09133827"],"award-info":[{"award-number":["IIRG09133827"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004100","name":"Labex","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004100","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL105756"],"award-info":[{"award-number":["R01 HL105756"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013258","name":"Hjartavernd","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013258","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["ADGC\u201310\u2013196728"],"award-info":[{"award-number":["ADGC\u201310\u2013196728"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2016,1]]},"abstract":"Abstract<\/jats:title>Introduction<\/jats:title>Few high penetrance variants that explain risk in late\u2010onset Alzheimer's disease (LOAD) families have been found.<\/jats:p><\/jats:sec>Methods<\/jats:title>We performed genome\u2010wide linkage and identity\u2010by\u2010descent (IBD) analyses on 41 non\u2010Hispanic white families exhibiting likely dominant inheritance of LOAD, and having no mutations at known familial Alzheimer's disease (AD) loci, and a low burden of APOE<\/jats:italic> \u03b54 alleles.<\/jats:p><\/jats:sec>Results<\/jats:title>Two\u2010point parametric linkage analysis identified 14 significantly linked regions, including three novel linkage regions for LOAD (5q32, 11q12.2\u201311q14.1, and 14q13.3), one of which replicates a genome\u2010wide association LOAD locus, the MS4A6A\u2010MS4A4E<\/jats:italic> gene cluster at 11q12.2. Five of the 14 regions (3q25.31, 4q34.1, 8q22.3, 11q12.2\u201314.1, and 19q13.41) are supported by strong multipoint results (logarithm of odds [LOD*] \u22651.5). Nonparametric multipoint analyses produced an additional significant locus at 14q32.2 (LOD* = 4.18). The 1\u2010LOD confidence interval for this region contains one gene, C14orf177<\/jats:italic>, and the microRNA Mir_320<\/jats:italic>, whereas IBD analyses implicates an additional gene BCL11B<\/jats:italic>, a regulator of brain\u2010derived neurotrophic signaling, a pathway associated with pathogenesis of several neurodegenerative diseases.<\/jats:p><\/jats:sec>Discussion<\/jats:title>Examination of these regions after whole\u2010genome sequencing may identify highly penetrant variants for familial LOAD.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2015.05.020","type":"journal-article","created":{"date-parts":[[2015,9,12]],"date-time":"2015-09-12T07:51:52Z","timestamp":1442044312000},"page":"2-10","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Genome\u2010wide linkage analyses of non\u2010Hispanic white families identify novel loci for familial late\u2010onset Alzheimer's disease"],"prefix":"10.1002","volume":"12","author":[{"given":"Brian W.","family":"Kunkle","sequence":"first","affiliation":[{"name":"John P. Hussman Institute for Human Genomics, Miller School of Medicine University of Miami Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Jaworski","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics, Miller School of Medicine University of Miami Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Barral","sequence":"additional","affiliation":[{"name":"The Taub Institute of Research on Alzheimer's Disease, College of Physicians and Surgeons Columbia University New York NY USA"},{"name":"The Gertrude H. Sergievsky Center, College of Physicians and Surgeons Columbia University New York NY USA"},{"name":"Department of Neurology, College of Physicians and Surgeons Columbia University New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Badri","family":"Vardarajan","sequence":"additional","affiliation":[{"name":"The Taub Institute of Research on Alzheimer's Disease, College of Physicians and Surgeons Columbia University New York NY USA"},{"name":"The Gertrude H. Sergievsky Center, College of Physicians and Surgeons Columbia University New York NY USA"},{"name":"Department of Psychiatry Washington University School of Medicine St. Louis MO USA"},{"name":"Hope Center for Neurological Disorders Department of Neurology Washington University School of Medicine St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary W.","family":"Beecham","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics, Miller School of Medicine University of Miami Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eden R.","family":"Martin","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics, Miller School of Medicine University of Miami Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura S.","family":"Cantwell","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Partch","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas D.","family":"Bird","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Washington Seattle WA USA"},{"name":"Department of Medicine University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy H.","family":"Raskind","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington Seattle WA USA"},{"name":"Department of Psychiatry and Behavioral Sciences University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita L.","family":"DeStefano","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Boston University School of Public Health Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina M.","family":"Carney","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics, Miller School of Medicine University of Miami Miami FL USA"},{"name":"Department of Psychiatry and Behavioral Sciences, Miller School of Medicine University of Miami Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Cuccaro","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics, Miller School of Medicine University of Miami Miami FL USA"},{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine University of Miami Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey M.","family":"Vance","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics, Miller School of Medicine University of Miami Miami FL USA"},{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine University of Miami Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay A.","family":"Farrer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Washington Seattle WA USA"},{"name":"Department of Medicine (Biomedical Genetics) Boston University School of Medicine and Public Health MA USA"},{"name":"Department of Neurology Boston University School of Medicine and Public Health MA USA"},{"name":"Department of Ophthalmology Boston University School of Medicine and Public Health MA USA"},{"name":"Department of Epidemiology Boston University School of Public Health MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison M.","family":"Goate","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine St. Louis MO USA"},{"name":"Hope Center for Neurological Disorders Department of Neurology Washington University School of Medicine St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Foroud","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard P.","family":"Mayeux","sequence":"additional","affiliation":[{"name":"The Taub Institute of Research on Alzheimer's Disease, College of Physicians and Surgeons Columbia University New York NY USA"},{"name":"The Gertrude H. Sergievsky Center, College of Physicians and Surgeons Columbia University New York NY USA"},{"name":"Department of Neurology, College of Physicians and Surgeons Columbia University New York NY USA"},{"name":"Department of Psychiatry, College of Physicians and Surgeons Columbia University New York NY USA"},{"name":"The Department of Epidemiology, School of Public Health Columbia University New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard D.","family":"Schellenberg","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan L.","family":"Haines","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Case Western Reserve University Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret A.","family":"Pericak\u2010Vance","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics, Miller School of Medicine University of Miami Miami FL USA"},{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine University of Miami Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,9,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2802"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31816b64dc"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000346826"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/hmg\/ddu372","article-title":"SUCLG2 identified as both a determinator of CSF A\u03b21\u201042 levels and an attenuator of cognitive decline in Alzheimer's disease","volume":"23","author":"Ramirez A","year":"2014","journal-title":"Hum Mol Genet"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11283"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211103"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211851"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000334381"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001308"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30590"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/423393"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.7156307"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1847"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng786"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.jalz.2015.07.487","article-title":"Linkage analyses in Caribbean Hispanic families identifies novel loci associated with familial late\u2010onset Alzheimer's disease","volume":"12","author":"Barral S","year":"2015","journal-title":"Alzheimer's Dement"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/gepi.1370030739","article-title":"Linkage probability and its approximate confidence interval under possible heterogeneity","volume":"257","author":"Ott J","year":"1986","journal-title":"Genet Epidemiol"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.2307\/2533202"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/301592"},{"key":"e_1_2_7_21_1","unstructured":"BoehnkeM PloughmanLM.SIMLINK: A Program for Estimating the Power of a Proposed Linkage Study by Computer Simulation. Version 4.12 1997."},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1086\/374823"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09534"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1195-241"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-1809.2001.6560577.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts609"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1934"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2012.00721.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.65.11.1518"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(00)00196-0"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.229102"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2012-13-9-r51"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-007-0103-3"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn233"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.112.963314"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0710263105"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e3283540394"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003652"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2450"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.17446611"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023691"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2009.54"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.142"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2013.00043"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/901082"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(97)00125-3"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.4781"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1912"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076001"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094961"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01038.x"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20539"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390051060"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1086\/518720"},{"key":"e_1_2_7_55_1","unstructured":"Alzheimer's Disease Sequencing Project (ADSP)2015. Available at:https:\/\/www.niagads.org\/adsp\/content\/home. Accessed August 29 2015."}],"container-title":["Alzheimer's & Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1552526015002241?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1552526015002241?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.jalz.2015.05.020","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.jalz.2015.05.020","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1016\/j.jalz.2015.05.020","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.jalz.2015.05.020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T19:48:04Z","timestamp":1759866484000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1016\/j.jalz.2015.05.020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,10]]},"references-count":54,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1016\/j.jalz.2015.05.020"],"URL":"https:\/\/doi.org\/10.1016\/j.jalz.2015.05.020","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,10]]},"assertion":[{"value":"2015-09-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}