Common variants at 6q22 and 17q21 are associated with intracranial volume

M Arfan Ikram, Myriam Fornage, Albert V Smith, Sudha Seshadri, Reinhold Schmidt, Stéphanie Debette, Henri A Vrooman, Sigurdur Sigurdsson, Stefan Ropele, H Rob Taal, Dennis O Mook-Kanamori, Laura H Coker, W T Longstreth, Wiro J Niessen, Anita L DeStefano, Alexa Beiser, Alex P Zijdenbos, Maksim Struchalin, Clifford R Jack, Fernando RivadeneiraAndre G Uitterlinden, David S Knopman, Anna-Liisa Hartikainen, Craig E Pennell, Elisabeth Thiering, Eric A P Steegers, Hakon Hakonarson, Joachim Heinrich, Lyle J Palmer, Marjo-Riitta Jarvelin, Mark I McCarthy, Struan F A Grant, Beate St Pourcain, Nicholas J Timpson, George Davey Smith, Ulla Sovio, Mike A Nalls, Rhoda Au, Albert Hofman, Haukur Gudnason, Aad van der Lugt, Tamara B Harris, William M Meeks, Meike W Vernooij, Mark A van Buchem, Diane Catellier, Vincent W V Jaddoe, Vilmundur Gudnason, B Gwen Windham, Philip A Wolf, Early Growth Genetics Consortium

Research output: Contribution to journalArticle (Academic Journal)peer-review

90 Citations (Scopus)


During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P <5 × 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 × 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 × 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 × 10(-3) for 6q22 and 1.2 × 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
Original languageEnglish
Pages (from-to)539-44
Number of pages6
JournalNature Genetics
Issue number5
Publication statusPublished - 2012


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