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

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; 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; Oliver S. P. Davis; Claire M. A. Haworth; Jennifer Pararajasingham; Thomas S. Price; Early Growth Genetics EGG Consorti; Cohorts Heart Aging Res Genomic Ep

doi:10.1038/ng.2245

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

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 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, Oliver S. P. Davis, Claire M. A. Haworth, Jennifer Pararajasingham, Thomas S. Price, Early Growth Genetics EGG Consorti, Cohorts Heart Aging Res Genomic Ep

^*Corresponding author for this work

Social Genetic & Developmental Psychiatry

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	N/A
Pages (from-to)	539-544
Number of pages	6
Journal	Nature Genetics
Volume	44
Issue number	5
DOIs	https://doi.org/10.1038/ng.2245
Publication status	Published - May 2012

Keywords

MATTER HYPERINTENSITY VOLUME
GENOME-WIDE ASSOCIATION
MICRODELETION SYNDROME
ALZHEIMERS-DISEASE
BRAIN
INVERSION
INTELLIGENCE
EVOLUTION
HAPLOTYPE
DEMENTIA

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Ikram, M. A., Fornage, M., Smith, A. V., Seshadri, S., Schmidt, R., Debette, S., Vrooman, H. A., Sigurdsson, S., Ropele, S., Taal, H. R., Mook-Kanamori, D. O., Coker, L. H., Longstreth, W. T., Niessen, W. J., DeStefano, A. L., Beiser, A., Zijdenbos, A. P., Struchalin, M., Jack, C. R., ... Cohorts Heart Aging Res Genomic Ep (2012). Common variants at 6q22 and 17q21 are associated with intracranial volume. Nature Genetics, 44(5), 539-544. Article N/A. https://doi.org/10.1038/ng.2245

@article{181200b8f0f14b008ca8a1b0e98d5322,

title = "Common variants at 6q22 and 17q21 are associated with intracranial volume",

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.",

keywords = "MATTER HYPERINTENSITY VOLUME, GENOME-WIDE ASSOCIATION, MICRODELETION SYNDROME, ALZHEIMERS-DISEASE, BRAIN, INVERSION, INTELLIGENCE, EVOLUTION, HAPLOTYPE, DEMENTIA",

author = "Ikram, {M. Arfan} and Myriam Fornage and Smith, {Albert V.} and Sudha Seshadri and Reinhold Schmidt and Stephanie Debette and Vrooman, {Henri A.} and Sigurdur Sigurdsson and Stefan Ropele and Taal, {H. Rob} and Mook-Kanamori, {Dennis O.} and Coker, {Laura H.} and Longstreth, {W. T.} and Niessen, {Wiro J.} and DeStefano, {Anita L.} and Alexa Beiser and Zijdenbos, {Alex P.} and Maksim Struchalin and Jack, {Clifford R.} and Fernando Rivadeneira and Uitterlinden, {Andre G.} and Knopman, {David S.} and Anna-Liisa Hartikainen and Pennell, {Craig E.} and Elisabeth Thiering and Steegers, {Eric A. P.} and Hakon Hakonarson and Joachim Heinrich and Palmer, {Lyle J.} and Marjo-Riitta Jarvelin and McCarthy, {Mark I.} and Grant, {Struan F. A.} and {St Pourcain}, Beate and Timpson, {Nicholas J.} and Smith, {George Davey} and Ulla Sovio and Nalls, {Mike A.} and Rhoda Au and Albert Hofman and Haukur Gudnason and {van der Lugt}, Aad and Harris, {Tamara B.} and Meeks, {William M.} and Vernooij, {Meike W.} and {van Buchem}, {Mark A.} and Diane Catellier and Davis, {Oliver S. P.} and Haworth, {Claire M. A.} and Jennifer Pararajasingham and Price, {Thomas S.} and {Early Growth Genetics EGG Consorti} and {Cohorts Heart Aging Res Genomic Ep}",

year = "2012",

month = may,

doi = "10.1038/ng.2245",

language = "English",

volume = "44",

pages = "539--544",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

}

Ikram, MA, Fornage, M, Smith, AV, Seshadri, S, Schmidt, R, Debette, S, Vrooman, HA, Sigurdsson, S, Ropele, S, Taal, HR, Mook-Kanamori, DO, Coker, LH, Longstreth, WT, Niessen, WJ, DeStefano, AL, Beiser, A, Zijdenbos, AP, Struchalin, M, Jack, CR, Rivadeneira, F, Uitterlinden, AG, Knopman, DS, Hartikainen, A-L, Pennell, CE, Thiering, E, Steegers, EAP, Hakonarson, H, Heinrich, J, Palmer, LJ, Jarvelin, M-R, McCarthy, MI, Grant, SFA, St Pourcain, B, Timpson, NJ, Smith, GD, Sovio, U, Nalls, MA, Au, R, Hofman, A, Gudnason, H, van der Lugt, A, Harris, TB, Meeks, WM, Vernooij, MW, van Buchem, MA, Catellier, D, Davis, OSP , Haworth, CMA , Pararajasingham, J , Price, TS, Early Growth Genetics EGG Consorti & Cohorts Heart Aging Res Genomic Ep 2012, 'Common variants at 6q22 and 17q21 are associated with intracranial volume', Nature Genetics, vol. 44, no. 5, N/A, pp. 539-544. https://doi.org/10.1038/ng.2245

TY - JOUR

T1 - Common variants at 6q22 and 17q21 are associated with intracranial volume

AU - Ikram, M. Arfan

AU - Fornage, Myriam

AU - Smith, Albert V.

AU - Seshadri, Sudha

AU - Schmidt, Reinhold

AU - Debette, Stephanie

AU - Vrooman, Henri A.

AU - Sigurdsson, Sigurdur

AU - Ropele, Stefan

AU - Taal, H. Rob

AU - Mook-Kanamori, Dennis O.

AU - Coker, Laura H.

AU - Longstreth, W. T.

AU - Niessen, Wiro J.

AU - DeStefano, Anita L.

AU - Beiser, Alexa

AU - Zijdenbos, Alex P.

AU - Struchalin, Maksim

AU - Jack, Clifford R.

AU - Rivadeneira, Fernando

AU - Uitterlinden, Andre G.

AU - Knopman, David S.

AU - Hartikainen, Anna-Liisa

AU - Pennell, Craig E.

AU - Thiering, Elisabeth

AU - Steegers, Eric A. P.

AU - Hakonarson, Hakon

AU - Heinrich, Joachim

AU - Palmer, Lyle J.

AU - Jarvelin, Marjo-Riitta

AU - McCarthy, Mark I.

AU - Grant, Struan F. A.

AU - St Pourcain, Beate

AU - Timpson, Nicholas J.

AU - Smith, George Davey

AU - Sovio, Ulla

AU - Nalls, Mike A.

AU - Au, Rhoda

AU - Hofman, Albert

AU - Gudnason, Haukur

AU - van der Lugt, Aad

AU - Harris, Tamara B.

AU - Meeks, William M.

AU - Vernooij, Meike W.

AU - van Buchem, Mark A.

AU - Catellier, Diane

AU - Davis, Oliver S. P.

AU - Haworth, Claire M. A.

AU - Pararajasingham, Jennifer

AU - Price, Thomas S.

AU - Early Growth Genetics EGG Consorti

AU - Cohorts Heart Aging Res Genomic Ep

PY - 2012/5

Y1 - 2012/5

N2 - 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.

AB - 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.

KW - MATTER HYPERINTENSITY VOLUME

KW - GENOME-WIDE ASSOCIATION

KW - MICRODELETION SYNDROME

KW - ALZHEIMERS-DISEASE

KW - BRAIN

KW - INVERSION

KW - INTELLIGENCE

KW - EVOLUTION

KW - HAPLOTYPE

KW - DEMENTIA

U2 - 10.1038/ng.2245

DO - 10.1038/ng.2245

M3 - Article

SN - 1061-4036

VL - 44

SP - 539

EP - 544

JO - Nature Genetics

JF - Nature Genetics

IS - 5

M1 - N/A

ER -

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

Abstract

Keywords

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