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

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

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Authors

  • M. Arfan Ikram
  • Myriam Fornage
  • Albert V. Smith
  • Sudha Seshadri
  • Reinhold Schmidt
  • Stephanie 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 Rivadeneira
  • And 110 others
  • Andre 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
  • Cornelia M. van Duijn
  • Thomas H. Mosley
  • Helena Schmidt
  • Lenore J. Launer
  • Monique M. B. Breteler
  • Charles DeCarli
  • Linda S. Adair
  • Wei Ang
  • Mustafa Atalay
  • Toos vanBeijsterveldt
  • Nienke Bergen
  • Kelly Benke
  • Diane Berry
  • Lachlan Coin
  • Oliver S. P. Davis
  • Paul Elliott
  • Claudia Flexeder
  • Tim Frayling
  • Romy Gaillard
  • Maria Groen-Blokhuis
  • Liang-Kee Goh
  • Claire M. A. Haworth
  • Dexter Hadley
  • Johannes Hedebrand
  • Anke Hinney
  • Joel N. Hirschhorn
  • John W. Holloway
  • Claus Holst
  • Jouke Jan Hottenga
  • Momoko Horikoshi
  • Ville Huikari
  • Elina Hypponen
  • Tuomas O. Kilpelainen
  • Mirna Kirin
  • Matthew Kowgier
  • Hanna-Maaria Lakka
  • Leslie A. Lange
  • Debbie A. Lawlor
  • Terho Lehtimaki
  • Alex Lewin
  • Cecilia Lindgren
  • Virpi Lindi
  • Reedik Maggi
  • Julie Marsh
  • Christel Middeldorp
  • Iona Millwood
  • Jeffrey C. Murray
  • Michel Nivard
  • Ellen Aagaard Nohr
  • Ioanna Ntalla
  • Emily Oken
  • Kalliope Panoutsopoulou
  • Jennifer Pararajasingham
  • Alina Rodriguez
  • Rany M. Salem
  • Sylvain Sebert
  • Niina Siitonen
  • David P. Strachan
  • Yik-Ying Teo
  • Beatriz Valcarcel
  • Gonneke Willemsen
  • Eleftheria Zeggini
  • Dorret I. Boomsma
  • Cyrus Cooper
  • Matthew Gillman
  • Berthold Hocher
  • Timo A. Lakka
  • Karen L. Mohlke
  • George V. Dedoussis
  • Ken K. Ong
  • Ewan R. Pearson
  • Thomas S. Price
  • Chris Power
  • Olli T. Raitakari
  • Seang-Mei Saw
  • Andre Scherag
  • Olli Simell
  • Thorkild I. A. Sorensen
  • James F. Wilson
  • Early Growth Genetics EGG Consorti, Cohorts Heart Aging Res Genomic Ep

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Info

Original languageEnglish
Pages539-544
Number of pages7
JournalNature Genetics
Journal publication dateMay 2012
Volume44
Issue5
DOIs
StatePublished

Abstract

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 &lt; 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 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 x 10(-3) for 6q22 and 1.2 x 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.</p>

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