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Stein JL, Medland SE, Vasquez AA, Hibar DP, Senstad RE, Winkler AM, Toro R, Appel K, Bartecek R, Bergmann Ř, Bernard M, Brown AA, Cannon DM, Chakravarty MM, Christoforou A, Domin M, Grimm O, Hollinshead M, Holmes AJ, Homuth G, Hottenga JJ, Langan C, Lopez LM, Hansell NK, Hwang KS, Kim S, Laje G, Lee PH, Liu X, Loth E, Lourdusamy A, Mattingsdal M, Mohnke S, Maniega SM, Nho K, Nugent AC, O'Brien C, Papmeyer M, Pütz B, Ramasamy A, Rasmussen J, Rijpkema M, Risacher SL, Roddey JC, Rose EJ, Ryten M, Shen L, Sprooten E, Strengman E, Teumer A, Trabzuni D, Turner J, van Eijk K, van Erp TG, van Tol MJ, Wittfeld K, Wolf C, Woudstra S, Aleman A, Alhusaini S, Almasy L, Binder EB, Brohawn DG, Cantor RM, Carless MA, Corvin A, Czisch M, Curran JE, Davies G, De Almeida MA, Delanty N, Depondt C, Duggirala R, Dyer TD, Erk S, Fagerness J, Fox PT, Freimer NB, Gill M, Göring HH, Hagler DJ, Hoehn D, Holsboer F, Hoogman M, Hosten N, Jahanshad N, Johnson MP, Kasperaviciute D, Kent JW, Kochunov P, Lancaster JL, Lawrie SM, Liewald DC, Mandl R, Matarin M, Mattheisen M, Meisenzahl E, Melle I, Moses EK, Mühleisen TW, Nauck M, Nöthen MM, Olvera RL, Pandolfo M, Pike GB, Puls R, Reinvang I, Rentería ME, Rietschel M, Roffman JL, Royle NA, Rujescu D, Savitz J, Schnack HG, Schnell K, Seiferth N, Smith C, Steen VM, Valdés Hernández MC, Van den Heuvel M, van der Wee NJ, Van Haren NE, Veltman JA, Völzke H, Walker R, Westlye LT, Whelan CD, Agartz I, Boomsma DI, Cavalleri GL, Dale AM, Djurovic S, Drevets WC, Hagoort P, Hall J, Heinz A, Jack CR, Foroud TM, Le Hellard S, Macciardi F, Montgomery GW, Poline JB, Porteous DJ, Sisodiya SM, Starr JM, Sussmann J, Toga AW, Veltman DJ, Walter H, Weiner MW, , , , , Bis JC, Ikram MA, Smith AV, Gudnason V, Tzourio C, Vernooij MW, Launer LJ, Decarli C, Seshadri S, , Andreassen OA, Apostolova LG, Bastin ME, Blangero J, Brunner HG, Buckner RL, Cichon S, Coppola G, de Zubicaray GI, Deary IJ, Donohoe G, de Geus EJ, Espeseth T, Fernández G, Glahn DC, Grabe HJ, Hardy J, Hulshoff Pol HE, Jenkinson M, Kahn RS, McDonald C, McIntosh AM, McMahon FJ, McMahon KL, Meyer-Lindenberg A, Morris DW, Müller-Myhsok B, Nichols TE, Ophoff RA, Paus T, Pausova Z, Penninx BW, Potkin SG, Sämann PG, Saykin AJ, Schumann G, Smoller JW, Wardlaw JM, Weale ME, Martin NG, Franke B, Wright MJ, Thompson PM, . Identification of common variants associated with human hippocampal and intracranial volumes. Nat Genet. 2012 ; 44(5):552-61. Pubmed Abstract

Comments on News and Primary Papers


Primary Papers: Identification of common variants associated with human hippocampal and intracranial volumes.

Comment by:  Patrick Sullivan, SRF Advisor
Submitted 20 April 2012
Posted 23 April 2012
  I recommend this paper

This is one of a series of three papers in Nature Genetics of relevance to students of the brain. It uses genomewide association studies of MRI phenotypes, with N's well in excess of 10,000.

This must be one of the most complex meta-analyses done in genetics. In addition to the now familiar issues of analyzing genetic data across multiple sites, the authors tackled harmonizing imaging phenotypes across many different scanners.

They identify robust and replicated candidate loci at levels of significance far smaller than chance. As is now familiar, the loci that emerge were rather unexpected, and not part of a typical list of "the usual suspects." How these loci influence MRI phenotypes could contain interesting biology.

It will be interesting to see if their findings do or do not line up with those from large studies of psychiatric disorders.

A much-debated issue in the field is whether imaging endophenotypes would prove to have simpler genetic architectures, perhaps characterized by larger effect sizes. The present studies do not support this conjecture. Indeed, imaging phenotypes seem to be rather typical complex traits. As the authors wrote:

"It has previously been hypothesized that brain imaging endo-phenotypes would have large effect sizes; however, this has proven not to be the case for the specific volumetric traits measured here, which had comparable effect sizes to those observed in other genome-wide association studies of complex traits (ref 40). Notably, the discovery sample had 99.92% power to detect variants with effect sizes of 1% of the variance for MAF ≥ 0.05."

View all comments by Patrick Sullivan