{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:21:36Z","timestamp":1790220096049,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,8,10]],"date-time":"2012-08-10T00:00:00Z","timestamp":1344556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>To identify novel late\u2010onset Alzheimer disease (LOAD) risk genes, we have analysed Amish populations of Ohio and Indiana. We performed genome\u2010wide SNP linkage and association studies on 798 individuals (109 with LOAD). We tested association using the Modified Quasi\u2010Likelihood Score test and also performed two\u2010point and multipoint linkage analyses. We found that LOAD was significantly associated with <jats:italic>APOE<\/jats:italic> (<jats:italic>P<\/jats:italic>= 9.0 \u00d7 10\u20136) in all our ascertainment regions except for the Adams County, Indiana, community (<jats:italic>P<\/jats:italic>= 0.55). Genome\u2010wide, the most strongly associated SNP was rs12361953 (<jats:italic>P<\/jats:italic>= 7.92 \u00d7 10\u20137). A very strong, genome\u2010wide significant multipoint peak [recessive heterogeneity multipoint LOD (HLOD) = 6.14, dominant HLOD = 6.05] was detected on 2p12. Three additional loci with multipoint HLOD scores &gt;3 were detected on 3q26, 9q31 and 18p11. Converging linkage and association results, the most significantly associated SNP under the 2p12 peak was at rs2974151 (<jats:italic>P<\/jats:italic>= 1.29 \u00d7 10\u20134). This SNP is located in <jats:italic>CTNNA2<\/jats:italic>, which encodes catenin alpha 2, a neuronal\u2010specific catenin known to have function in the developing brain. These results identify <jats:italic>CTNNA2<\/jats:italic> as a novel candidate LOAD gene, and implicate three other regions of the genome as novel LOAD loci. These results underscore the utility of using family\u2010based linkage and association analyses in isolated populations to identify novel loci for traits with complex genetic architecture.<\/jats:p>","DOI":"10.1111\/j.1469-1809.2012.00721.x","type":"journal-article","created":{"date-parts":[[2012,8,10]],"date-time":"2012-08-10T09:52:13Z","timestamp":1344592333000},"page":"342-351","source":"Crossref","is-referenced-by-count":45,"title":["Genome\u2010Wide Association and Linkage Study in the Amish Detects a Novel Candidate Late\u2010Onset Alzheimer Disease Gene"],"prefix":"10.1111","volume":"76","author":[{"given":"Anna C.","family":"Cummings","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Digna R.","family":"Velez Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob L.","family":"McCauley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Laux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne L.","family":"McFarland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Fuzzell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Knebusch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Caywood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Reinhart\u2010Mercer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Nations","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Gilbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Konidari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tramontana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Cuccaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William K.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Pericak\u2010Vance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan L.","family":"Haines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,8,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng786"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.20004"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990910)86:2<156::AID-AJMG13>3.0.CO;2-5"},{"key":"e_1_2_6_5_1","volume-title":"Amish and Mennonites in Eastern Elkhart & LaGrange Counties, Indiana 1841\u20131991. 2nd printing","author":"Amish Heritage Committee","year":"2009"},{"key":"e_1_2_6_6_1","volume-title":"Unser Leit: the story of the Amish","author":"Beachy L.","year":"2011"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.10.013"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000087122"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2011.00658.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30257"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm224"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.440"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.803"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.56021\/9780801844416"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.237"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.439"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/518720"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2006.00279.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.24"},{"key":"e_1_2_6_20_1","first-page":"19","article-title":"Combinatorial Mismatch Scan (CMS) for loci associated with dementia in the Amish. BMC","volume":"7","author":"McCauley J. L.","year":"2006","journal-title":"Med Genet"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.39.9.1159"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.801"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng908"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390605"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.574"},{"key":"e_1_2_6_27_1","first-page":"314","article-title":"The modified mini\u2010mental state (3MS) examination","volume":"48","author":"Teng E. L.","year":"1987","journal-title":"J Clin Psychiatry"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1086\/519497"},{"key":"e_1_2_6_29_1","first-page":"28","article-title":"An adaptation of the modified mini\u2010mental state examination: analysis of demographic influences and normative data: the cache county study. Neuropsychiatry Neuropsychol","volume":"15","author":"Tschanz J. T.","year":"2002","journal-title":"Behav Neurol"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/27208"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1469-1809.2012.00721.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1469-1809.2012.00721.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T05:27:48Z","timestamp":1698730068000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1469-1809.2012.00721.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,10]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,9]]}},"alternative-id":["10.1111\/j.1469-1809.2012.00721.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1469-1809.2012.00721.x","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"value":"0003-4800","type":"print"},{"value":"1469-1809","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,10]]}}}