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PLoS One. 2013 Aug 28;8(8):e71723. doi: 10.1371/journal.pone.0071723. eCollection 2013.

Mapping the genetic variation of regional brain volumes as explained by all common SNPs from the ADNI study.

Collaborators (321)

Weiner M, Aisen P, Petersen R, Jack CR Jr, Jagust W, Trojanowki JQ, Toga AW, Beckett L, Green RC, Saykin AJ, Morris J, Shaw LM, Khachaturian Z, Sorensen G, Carrillo M, Kuller L, Raichle M, Paul S, Davies P, Fillit H, Hefti F, Holtzman D, Mesulam M, Potter W, Snyder P, Schwartz A, Green RC, Montine T, Petersen R, Aisen P, Thomas RG, Donohue M, Walter S, Gessert D, Sather T, Jiminez G, Beckett L, Harvey D, Donohue M, Bernstein M, Fox N, Thompson P, Schuff N, DeCArli C, Borowski B, Gunter J, Senjem M, Vemuri P, Jones D, Kantarci K, Ward C, Jagust W, Koeppe RA, Foster N, Reiman EM, Chen K, Mathis C, Landau S, Morris JC, Cairns NJ, Householder E, Taylor-Reinwald L, Shaw LM, Trojanowki JQ, Lee V, Korecka M, Figurski M, Toga AW, Crawford K, Neu S, Saykin AJ, Foroud TM, Potkin S, Shen L, Faber K, Kim S, Nho K, Weiner MW, Thal L, Khachaturian Z, Thal L, Buckholtz N, Weiner MW, Snyder PJ, Potter W, Paul S, Albert M, Frank R, Khachaturian Z, Hsiao J, Kaye J, Quinn J, Lind B, Carter R, Dolen S, Schneider LS, Pawluczyk S, Beccera M, Teodoro L, Spann BM, Brewer J, Vanderswag H, Fleisher A, Heidebrink JL, Lord JL, Petersen R, Mason SS, Albers CS, Knopman D, Johnson K, Doody RS, Villanueva-Meyer J, Chowdhury M, Rountree S, Dang M, Stern Y, Honig LS, Bell KL, Ances B, Morris JC, Carroll M, Leon S, Householder E, Mintun MA, Schneider S, Oliver A, Marson D, Griffith R, Clark D, Geldmacher D, Brockington J, Roberson E, Grossman H, Mitsis E, deToledo-Morrell L, Shah RC, Duara R, Varon D, Greig MT, Roberts P, Albert M, Onyike C, D' Agostino D 2nd, Kielb S, Galvin JE, Pogorelec DM, Cerbone B, Michel CA, Rusinek H, de Leon MJ, Glodzik L, De Santi S, Doraiswamy P, Petrella JR, Wong TZ, Arnold SE, Karlawish JH, Wolk D, Smith CD, Jicha G, Hardy P, Sinha P, Oates E, Conrad G, Lopez OL, Oakley M, Simpson DM, Porsteinsson AP, Goldstein BS, Martin K, Makino KM, Ismail M, Brand C, Mulnard RA, Thai G, Mc-Adams-Ortiz C, Womack K, Mathews D, Quiceno M, Diaz-Arrastia R, King R, Weiner M, Martin-Cook K, DeVous M, Levey AI, Lah JJ, Cellar JS, Burns JM, Anderson HS, Swerdlow RH, Apostolova L, Tingus K, Woo E, Silverman DH, Lu PH, Bartzokis G, Graff-Radford NR, Parfitt F, Kendall T, Johnson H, Farlow MR, Hake AM, Matthews BR, Hunt C, van Dyck CH, Carson RE, MacAvoy MG, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Hsiung R, Feldman H, Mudge B, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Kerwin D, Mesulam MM, Lipowski K, Wu CK, Johnson N, Sadowsky C, Martinez W, Villena T, Turner RS, Johnson K, Sperling RA, Johnson KA, Marshall G, Frey M, Yesavage J, Taylor L, Lane B, Rosen A, Tinklenberg J, Sabbagh MN, Belden CM, Jacobson SA, Sirrel SA, Kowall N, Killiany R, Budson AE, Norbash A, Johnson PL, Obisesan TO, Wolday S, Allard J, Lerner A, Ogrocki P, Hudson L, Fletcher E, Carmichael O, Olichney J, DeCarli C, Kittur S, Borrie M, Lee TY, Bartha R, Johnson S, Asthana S, Carlsson CM, Potkin SG, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Scharre DW, Kataki M, Adeli A, Zimmerman EA, Celmins D, Brown AD, Pearlson GD, Blank K, Anderson K, Santulli RB, Kitzmiller TJ, Schwartz ES, Sink KM, Williamson JD, Garg P, Watkins F, Ott BR, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen HJ, Miller BL, Mintzer J, Spicer K, Bachman D, Pasternak S, Rachinsky I, Rogers J, Kertesz A, Drost D, Pomara N, Hernando R, Sarrael A, Schultz SK, Ponto LL, Shim H, Smith KE, Relkin N, Chaing G, Raudin L, Smith A, Fargher K, Raj BA.

Author information

1
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

Abstract

Typically twin studies are used to investigate the aggregate effects of genetic and environmental influences on brain phenotypic measures. Although some phenotypic measures are highly heritable in twin studies, SNPs (single nucleotide polymorphisms) identified by genome-wide association studies (GWAS) account for only a small fraction of the heritability of these measures. We mapped the genetic variation (the proportion of phenotypic variance explained by variation among SNPs) of volumes of pre-defined regions across the whole brain, as explained by 512,905 SNPs genotyped on 747 adult participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We found that 85% of the variance of intracranial volume (ICV) (p = 0.04) was explained by considering all SNPs simultaneously, and after adjusting for ICV, total grey matter (GM) and white matter (WM) volumes had genetic variation estimates near zero (p = 0.5). We found varying estimates of genetic variation across 93 non-overlapping regions, with asymmetry in estimates between the left and right cerebral hemispheres. Several regions reported in previous studies to be related to Alzheimer's disease progression were estimated to have a large proportion of volumetric variance explained by the SNPs.

PMID:
24015190
PMCID:
PMC3756017
DOI:
10.1371/journal.pone.0071723
[Indexed for MEDLINE]
Free PMC Article
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