Common Variants at 6q22 and 17q21 Are Associated with Intracranial Volume

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Ikram, M. Arfan; Fornage, Myriam; Smith, Albert V.; Seshadri, Sudha; Schmidt, Reinhold; Debette, Stephanie; Vrooman, Henri A.; Sigurdsson, Sigurdur; Ropele, Stefan; & Taal, H. Rob, et al. (2012). Common Variants at 6q22 and 17q21 Are Associated with Intracranial Volume. Nature Genetics, 44(5), 539-544. PMCID: PMC3618290

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 < 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.

URL

http://dx.doi.org/10.1038/ng.2245

Reference Type

Journal Article

Year Published

2012

Journal Title

Nature Genetics

Author(s)

Ikram, M. Arfan
Fornage, Myriam
Smith, Albert V.
Seshadri, Sudha
Schmidt, Reinhold
Debette, Stephanie
Vrooman, Henri A.
Sigurdsson, Sigurdur
Ropele, Stefan
Taal, H. Rob
Mook-Kanamori, Dennis O.
Coker, Laura H.
Longstreth, W. T., Jr.
Niessen, Wiro J.
DeStefano, Anita L.
Beiser, Alexa
Zijdenbos, Alex P.
Struchalin, Maksim
Jack, Clifford R., Jr.
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.
St. Pourcain, Beate
Timpson, Nicholas J.
Smith, George Davey
Sovio, Ulla
The Early Growth Genetics (EGG) Consortium, [
Linda S. Adair, Member
]
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 J.
Jaddoe, Vincent W. V.
Gudnason, Vilmundur G.
Windham, Beverly G.
Wolf, Philip A.
van Duijn, Cornelia M.
Mosley, Thomas H., Jr.
Schmidt, Helena
Launer, Lenore J.
Breteler, Monique M. B.
DeCarli, Charles S., for The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

PMCID

PMC3618290