The University of Southampton
University of Southampton Institutional Repository

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

Ikram, M. Arfan, Fornage, Myriam, Smith, Albert V., Seshadri, Sudha, Schmidt, Reinhold, Debette, Stéphanie, Vrooman, Henri A., Sigurdsson, Sigurdur, Ropele, Stefan, Taal, H. Rob, Mook-Kanamori, Dennis O., Coker, Laura H., Longstreth, W.T., Niessen, Wiro J., DeStefano, Anita L., Beiser, Alexa, Zijdenbos, Alex P., Struchalin, Maksim, Jack, Clifford R., Rivadeneira, Fernando, Uitterlinden, Andre G., Knopman, David S., Hartikainen, Anna-Liisa, Pennell, Craig E., Thiering, Elisabeth, Steegers, Eric A.P., Hakonarson, Hakon, Heinrich, Joachim, Palmer, Lyle J., Jarvelin, Marjo-Riitta, McCarthy, Mark I., Grant, Struan F.A., Pourcain, Beate St, Timpson, Nicholas J., Smith, George Davey, Sovio, Ulla, Nalls, Mike A., Au, Rhoda, Hofman, Albert, Gudnason, Haukur, van der Lugt, Aad, Harris, Tamara B., Meeks, William M., Vernooij, Meike W., van Buchem, Mark A., Catellier, Diane, Jaddoe, Vincent W.V., Gudnason, Vilmundur, Windham, B. Gwen, Wolf, Philip A., van Duijn, Cornelia M., Mosley, Thomas H., Schmidt, Helena, Launer, Lenore J., Breteler, Monique M.B., DeCarli, Charles, Adair, Linda S., Ang, Wei, Atalay, Mustafa, van Beijsterveldt, Toos, Bergen, Nienke, Benke, Kelly, Berry, Diane, Coin, Lachlan, Davis, Oliver S.P., Elliott, Paul, Flexeder, Claudia, Frayling, Tim, Gaillard, Romy, Groen-Blokhuis, Maria, Goh, Liang-Kee, Haworth, Claire M.A., Hadley, Dexter, Hedebrand, Johannes, Hinney, Anke, Hirschhorn, Joel N., Holloway, John W., Holst, Claus, Jan Hottenga, Jouke, Horikoshi, Momoko, Huikari, Ville, Hypponen, Elina, Kilpeläinen, Tuomas O., Kirin, Mirna, Kowgier, Matthew, Lakka, Hanna-Maaria, Lange, Leslie A., Lawlor, Debbie A., Lehtimäki, Terho, Lewin, Alex, Lindgren, Cecilia, Lindi, Virpi, Maggi, Reedik, Marsh, Julie, Middeldorp, Christel, Millwood, Iona, Murray, Jeffrey C., Nivard, Michel, Nohr, Ellen Aagaard, Ntalla, Ioanna, Oken, Emily, Panoutsopoulou, Kalliope, Pararajasingham, Jennifer, Rodriguez, Alina, Salem, Rany M., Sebert, Sylvain, Siitonen, Niina, Strachan, David P., Teo, Yik-Ying, Valcárcel, Beatriz, Willemsen, Gonneke, Zeggini, Eleftheria, Boomsma, Dorret I., Cooper, Cyrus, Gillman, Matthew, Hocher, Berthold, Lakka, Timo A., Mohlke, Karen L., Dedoussis, George V., Ong, Ken K., Pearson, Ewan R., Price, Thomas S., Power, Chris, Raitakari, Olli T., Saw, Seang-Mei, Scherag, Andre, Simell, Olli, Sørensen, Thorkild I.A. and Wilson, James F. (2012) Common variants at 6q22 and 17q21 are associated with intracranial volume Nature Genetics, 44, (5), pp. 539-544. (doi:10.1038/ng.2245). (PMID:22504418).

Record type: Article


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.

Full text not available from this repository.

More information

e-pub ahead of print date: 15 April 2012
Organisations: Human Development & Health


Local EPrints ID: 337512
ISSN: 1061-4036
PURE UUID: cae73a50-dc5c-44c3-bdb5-b8b1fe728dae
ORCID for John W. Holloway: ORCID iD
ORCID for Cyrus Cooper: ORCID iD

Catalogue record

Date deposited: 26 Apr 2012 12:08
Last modified: 18 Jul 2017 06:02

Export record



Author: M. Arfan Ikram
Author: Myriam Fornage
Author: Albert V. Smith
Author: Sudha Seshadri
Author: Reinhold Schmidt
Author: Stéphanie Debette
Author: Henri A. Vrooman
Author: Sigurdur Sigurdsson
Author: Stefan Ropele
Author: H. Rob Taal
Author: Dennis O. Mook-Kanamori
Author: Laura H. Coker
Author: W.T. Longstreth
Author: Wiro J. Niessen
Author: Anita L. DeStefano
Author: Alexa Beiser
Author: Alex P. Zijdenbos
Author: Maksim Struchalin
Author: Clifford R. Jack
Author: Fernando Rivadeneira
Author: Andre G. Uitterlinden
Author: David S. Knopman
Author: Anna-Liisa Hartikainen
Author: Craig E. Pennell
Author: Elisabeth Thiering
Author: Eric A.P. Steegers
Author: Hakon Hakonarson
Author: Joachim Heinrich
Author: Lyle J. Palmer
Author: Marjo-Riitta Jarvelin
Author: Mark I. McCarthy
Author: Struan F.A. Grant
Author: Beate St Pourcain
Author: Nicholas J. Timpson
Author: George Davey Smith
Author: Ulla Sovio
Author: Mike A. Nalls
Author: Rhoda Au
Author: Albert Hofman
Author: Haukur Gudnason
Author: Aad van der Lugt
Author: Tamara B. Harris
Author: William M. Meeks
Author: Meike W. Vernooij
Author: Mark A. van Buchem
Author: Diane Catellier
Author: Vincent W.V. Jaddoe
Author: Vilmundur Gudnason
Author: B. Gwen Windham
Author: Philip A. Wolf
Author: Cornelia M. van Duijn
Author: Thomas H. Mosley
Author: Helena Schmidt
Author: Lenore J. Launer
Author: Monique M.B. Breteler
Author: Charles DeCarli
Author: Linda S. Adair
Author: Wei Ang
Author: Mustafa Atalay
Author: Toos van Beijsterveldt
Author: Nienke Bergen
Author: Kelly Benke
Author: Diane Berry
Author: Lachlan Coin
Author: Oliver S.P. Davis
Author: Paul Elliott
Author: Claudia Flexeder
Author: Tim Frayling
Author: Romy Gaillard
Author: Maria Groen-Blokhuis
Author: Liang-Kee Goh
Author: Claire M.A. Haworth
Author: Dexter Hadley
Author: Johannes Hedebrand
Author: Anke Hinney
Author: Joel N. Hirschhorn
Author: Claus Holst
Author: Jouke Jan Hottenga
Author: Momoko Horikoshi
Author: Ville Huikari
Author: Elina Hypponen
Author: Tuomas O. Kilpeläinen
Author: Mirna Kirin
Author: Matthew Kowgier
Author: Hanna-Maaria Lakka
Author: Leslie A. Lange
Author: Debbie A. Lawlor
Author: Terho Lehtimäki
Author: Alex Lewin
Author: Cecilia Lindgren
Author: Virpi Lindi
Author: Reedik Maggi
Author: Julie Marsh
Author: Christel Middeldorp
Author: Iona Millwood
Author: Jeffrey C. Murray
Author: Michel Nivard
Author: Ellen Aagaard Nohr
Author: Ioanna Ntalla
Author: Emily Oken
Author: Kalliope Panoutsopoulou
Author: Jennifer Pararajasingham
Author: Alina Rodriguez
Author: Rany M. Salem
Author: Sylvain Sebert
Author: Niina Siitonen
Author: David P. Strachan
Author: Yik-Ying Teo
Author: Beatriz Valcárcel
Author: Gonneke Willemsen
Author: Eleftheria Zeggini
Author: Dorret I. Boomsma
Author: Cyrus Cooper ORCID iD
Author: Matthew Gillman
Author: Berthold Hocher
Author: Timo A. Lakka
Author: Karen L. Mohlke
Author: George V. Dedoussis
Author: Ken K. Ong
Author: Ewan R. Pearson
Author: Thomas S. Price
Author: Chris Power
Author: Olli T. Raitakari
Author: Seang-Mei Saw
Author: Andre Scherag
Author: Olli Simell
Author: Thorkild I.A. Sørensen
Author: James F. Wilson

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.