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 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; Vincent W V Jaddoe; Vilmundur Gudnason; B Gwen Windham; Philip A Wolf; Early Growth Genetics Consortium

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, 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 journal › Article (Academic Journal) › peer-review

100 Citations (Scopus)

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

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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., ... Early Growth Genetics Consortium (2012). Common variants at 6q22 and 17q21 are associated with intracranial volume. Nature Genetics, 44(5), 539-44. https://doi.org/10.1038/ng.2245

@article{0f319d1b846f4b27ab729d4273243ba1,

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 × 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.",

author = "Ikram, \{M Arfan\} and Myriam Fornage and Smith, \{Albert V\} and Sudha Seshadri and Reinhold Schmidt and St{\'e}phanie 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 Jaddoe, \{Vincent W V\} and Vilmundur Gudnason and Windham, \{B Gwen\} and Wolf, \{Philip A\} and \{Early Growth Genetics Consortium\}",

year = "2012",

doi = "10.1038/ng.2245",

language = "English",

volume = "44",

pages = "539--44",

journal = "Nature Genetics",

issn = "1546-1718",

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, Jaddoe, VWV, Gudnason, V, Windham, BG, Wolf, PA & Early Growth Genetics Consortium 2012, 'Common variants at 6q22 and 17q21 are associated with intracranial volume', Nature Genetics, vol. 44, no. 5, pp. 539-44. 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, Stéphanie

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 - Jaddoe, Vincent W V

AU - Gudnason, Vilmundur

AU - Windham, B Gwen

AU - Wolf, Philip A

AU - Early Growth Genetics Consortium

PY - 2012

Y1 - 2012

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 × 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.

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 × 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.

U2 - 10.1038/ng.2245

DO - 10.1038/ng.2245

M3 - Article (Academic Journal)

C2 - 22504418

SN - 1546-1718

VL - 44

SP - 539

EP - 544

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

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

Abstract

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