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PLoS One. 2013 Nov 7;8(11):e79771. doi: 10.1371/journal.pone.0079771. eCollection 2013.

Alzheimer's disease: analyzing the missing heritability.

Collaborators (168)

Albert MS, Albin RL, Apostolova LG, Arnold SE, Baldwin CT, Barber R, Barmada MM, Barnes LL, Beach TG, Beecham GW, Beekly D, Bennett DA, Bigio EH, Bird TD, Blacker D, Boeve BF, Bowen JD, Boxer A, Burke JR, Buxbaum JD, Cairns NJ, Cantwell LB, Cao C, Carlson CS, Carney RM, Carrasquillo MM, Carroll SL, Chui HC, Clark DG, Corneveaux J, Crane PK, Cribbs DH, Crocco EA, Cruchaga C, De Jager PL, DeCarli C, DeKosky ST, Demirci F, Dick M, Dickson DW, Duara R, Ertekin-Taner N, Evans D, Faber KM, Fallon KB, Farlow MR, Farrer LA, Ferris S, Foroud TM, Frosch MP, Galasko DR, Ganguli M, Gearing M, Geschwind DH, Ghetti B, Gilbert JR, Gilman S, Glass JD, Goate AM, Graff-Radford NR, Green RC, Growdon JH, Haines JL, Hakonarson H, Hamilton-Nelson KL, Hamilton RL, Hardy J, Harrell LE, Head E, Honig LS, Huentelman MJ, Hulette CM, Hyman BT, Jarvik GP, Jicha GA, Jin LW, Jun G, Kamboh M, Karydas A, Kauwe JS, Kaye JA, Kim R, Koo EH, Kowall NW, Kramer JH, Kramer P, Kukull WA, LaFerla FM, Lah JJ, Larson EB, Leverenz JB, Levey AI, Li G, Lieberman AP, Lin CF, Lopez OL, Lunetta KL, Lyketsos CG, Mack WJ, Marson DC, Martin ER, Martiniuk F, Mash DC, Masliah E, Mayeux R, McCormick WC, McCurry SM, McDavid AN, McKee AC, Mesulam M, Miller BL, Miller CA, Miller JW, Montine TJ, Morris JC, Murrell JR, Myers AJ, Naj AC, Olichney JM, Pankratz VS, Parisi JE, Pericak-Vance MA, Peskind E, Petersen RC, Pierce A, Poon WW, Potter H, Quinn JF, Raj A, Raskind M, Reiman EM, Reisberg B, Reitz C, Ringman JM, Roberson ED, Rogaeva E, Rosen HJ, Rosenberg RN, Sano M, Saykin AJ, Schellenberg GD, Schneider JA, Schneider LS, Seeley WW, Smith AG, Sonnen JA, Spina S, George-Hyslop PS, Stern RA, Tanzi RE, Trojanowski JQ, Troncoso JC, Tsuang DW, Valladares O, Van Deerlin VM, Van Eldik LJ, Vardarajan BN, Vinters HV, Vonsattel JP, Wang LS, Weintraub S, Welsh-Bohmer KA, Williamson J, Woltjer RL, Wright CB, Younkin SG, Yu CE, Yu L.

Author information

1
Department of Biology, Brigham Young University, Provo, Utah, United States of America ; ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah, United States of America.

Abstract

Alzheimer's disease (AD) is a complex disorder influenced by environmental and genetic factors. Recent work has identified 11 AD markers in 10 loci. We used Genome-wide Complex Trait Analysis to analyze >2 million SNPs for 10,922 individuals from the Alzheimer's Disease Genetics Consortium to assess the phenotypic variance explained first by known late-onset AD loci, and then by all SNPs in the Alzheimer's Disease Genetics Consortium dataset. In all, 33% of total phenotypic variance is explained by all common SNPs. APOE alone explained 6% and other known markers 2%, meaning more than 25% of phenotypic variance remains unexplained by known markers, but is tagged by common SNPs included on genotyping arrays or imputed with HapMap genotypes. Novel AD markers that explain large amounts of phenotypic variance are likely to be rare and unidentifiable using genome-wide association studies. Based on our findings and the current direction of human genetics research, we suggest specific study designs for future studies to identify the remaining heritability of Alzheimer's disease.

PMID:
24244562
PMCID:
PMC3820606
DOI:
10.1371/journal.pone.0079771
[Indexed for MEDLINE]
Free PMC Article

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