{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:25:40Z","timestamp":1791264340489,"version":"4.1.0"},"reference-count":16,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5500","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2000,12,22]]},"abstract":"<jats:p>\n            The apolipoprotein E (\n            <jats:italic>APOE<\/jats:italic>\n            ) gene is the only genetic risk factor that has so far been linked to risk for late-onset Alzheimer's disease (LOAD). However, 50 percent of Alzheimer's disease cases do not carry an\n            <jats:italic>APOE4<\/jats:italic>\n            allele, suggesting that other risk factors must exist. We performed a two-stage genome-wide screen in sibling pairs with LOAD to detect other susceptibility loci. Here we report evidence for an Alzheimer's disease locus on chromosome 10. Our stage one multipoint lod score (logarithm of the odds ratio for linkage\/no linkage) of 2.48 (266 sibling pairs) increased to 3.83 in stage 2 (429 sibling pairs) close to D10S1225 (79 centimorgans). This locus modifies risk for Alzheimer's disease independent of\n            <jats:italic>APOE<\/jats:italic>\n            genotype.\n          <\/jats:p>","DOI":"10.1126\/science.290.5500.2304","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:47:44Z","timestamp":1027763264000},"page":"2304-2305","source":"Crossref","is-referenced-by-count":288,"title":["Susceptibility Locus for Alzheimer's Disease on Chromosome 10"],"prefix":"10.1126","volume":"290","author":[{"given":"Amanda","family":"Myers","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Holmans","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dzanan","family":"Ramic","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shantia","family":"Shears","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Booth","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne Wavrant","family":"DeVrieze","sequence":"additional","affiliation":[{"name":"Laboratory for Neurogenetics, Birdsall Building, Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Crook","sequence":"additional","affiliation":[{"name":"Laboratory for Neurogenetics, Birdsall Building, Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Hamshere","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Abraham","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Tunstall","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE58AF, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Rice","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Carty","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lillystone","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pat","family":"Kehoe","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varuni","family":"Rudrasingham","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lovestone","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE58AF, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Perez-Tur","sequence":"additional","affiliation":[{"name":"Unitat de Gene\u0300tica Molecular, Institut de Biomedicina de Vale\u0300ncia-CSIC, E-46010 Vale\u0300ncia, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hardy","sequence":"additional","affiliation":[{"name":"Laboratory for Neurogenetics, Birdsall Building, Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M.","family":"Goate","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1001\/jama.1997.03540340059034","volume":"227","author":"Lendon C. L.","year":"1997","unstructured":"Lendon C. L., Ashall F., Goate A., JAMA 227, 825 (1997).","journal-title":"JAMA"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0896-864"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","volume":"278","author":"Farrer L.","year":"1997","unstructured":"Farrer L., et al., JAMA 278, 1349 (1997).","journal-title":"JAMA"},{"key":"e_1_3_1_6_2","unstructured":"Many data and biomaterials were collected in three projects that participated in the National Institute of Mental Health (NIMH) Alzheimer's Disease Genetics Initiative. From 1991 to 1998 the principal investigators and coinvestigators were as follows: Massachusetts General Hospital Boston MA U01 MH46281 Marilyn S. Albert and Deborah Blacker; Johns Hopkins University Baltimore MD U01 MH46290 Susan Bassett Gary A. Chase and Marshal F. Folstein; and University of Alabama Birmingham AL U01 MH46373 Rodney C. P. Go and Lindy E. Harrell."},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1093\/hmg\/8.2.237","volume":"8","author":"Kehoe P.","year":"1999","unstructured":"Kehoe P., et al., Hum. Mol. Genet. 8, 237 (1999).","journal-title":"Hum. Mol. Genet."},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1195-241"},{"key":"e_1_3_1_9_2","unstructured":"See Web table 1 for sample characteristics (14)."},{"key":"e_1_3_1_10_2","first-page":"1221","volume":"57","author":"Holmans P.","year":"1995","unstructured":"Holmans P., Clayton D., Am. J. Hum. Genet. 57, 1221 (1995).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_1_11_2","unstructured":"See Web table 2 for two-point lod scores and allele sharing identical-by-descent (IBD) sharing (15)."},{"key":"e_1_3_1_12_2","first-page":"1347","volume":"58","author":"Kruglyak L.","year":"1995","unstructured":"Kruglyak L., Lander E., Am. J. Hum. Genet. 58, 1347 (1995).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_1_13_2","unstructured":"Accurate estimates of genome-wide significance were obtained by repeating the analysis on replicate \u201cgenomes\u201d simulated in the absence of a disease locus with the observed marker maps allele frequencies and typed individuals. For more details on the method see N. M. Williams et al. [ Hum. Mol. Genet. 8 1729 (1999)]."},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1126\/science.290.5500.2303","volume":"290","author":"Ertekin-Taner N.","year":"2000","unstructured":"Ertekin-Taner N., et al., Science 290, 2303 (2000).","journal-title":"Science"},{"key":"e_1_3_1_15_2","unstructured":"Supplementary material is available at www.sciencemag.org\/cgi\/content\/full\/290\/5500\/2304\/DC1."},{"key":"e_1_3_1_16_2","unstructured":"See www.marshmed.org\/genetics\/mapmarkers\/maps\/indexmap.html."},{"key":"e_1_3_1_17_2","unstructured":"J.W. M.J.O. and S.L. are supported by the UK Medical Research Council. A.M.G. and J.H. are supported by NIH grants AG16208 and AG5681. A.M.G. was supported by the Nettie and Rebecca Brown Fund. We thank the families who participated in this study."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.290.5500.2304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T09:55:45Z","timestamp":1705139745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.290.5500.2304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,12,22]]},"references-count":16,"journal-issue":{"issue":"5500","published-print":{"date-parts":[[2000,12,22]]}},"alternative-id":["10.1126\/science.290.5500.2304"],"URL":"https:\/\/doi.org\/10.1126\/science.290.5500.2304","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,12,22]]}}}