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

Arfan Ikram; M Fornage; AV Smith; S Seshadri; R Schmidt; S Debette; Henri Vrooman; S Sigurdsson; S Ropele; Rob Taal; Dennis Mook; LH Coker; WT Longstreth; Wiro Niessen; AL DeStefano; A Beiser; AP Zijdenbos; M Struchalin; CR Jack; Fernando Rivadeneira; André Uitterlinden; DS Knopman; AL Hartikainen; CE Pennell; E Thiering; Eric Steegers; H Hakonarson; J (Joachim) Heinrich; LJ Palmer; MR Jarvelin; MI McCarthy; SFA Grant; B St Pourcain; NJ Timpson; GD Smith; U Sovio; MA Nalls; R (Rhoda) Au; Bert Hofman; H Gudnason; Aad van der Lugt; TB Harris; WM Meeks; Meike Vernooij; MA van Buchem; D Catellier; Vincent Jaddoe; V Gudnason; BG Windham; PA Wolf; Cornelia Duijn; TH Mosley; Heléna Schmidt; LJ (Lenore) Launer; Monique Breteler; C DeCarli; LS Adair; W Ang; M Atalay; T vanBeijsterveldt; N Bergen; K Benke; D Berry; L Coin; OSP Davis; P Elliott; C Flexeder; T Frayling; Romy Gaillard; M Groen-Blokhuis; LK Goh; CMA Haworth; D Hadley; J Hedebrand; A Hinney; JN Hirschhorn; JW Holloway; C Holst; JJ (Jouke Jan) Hottenga; M Horikoshi; V Huikari; E Hypponen; TO Kilpelainen; M Kirin; M Kowgier; HM Lakka; LA Lange; DA Lawlor; T Lehtimaki; A Lewin; C Lindgren; V Lindi; R Maggi; J Marsh; C Middeldorp; I Millwood; JC Murray; M Nivard; EA Nohr; I Ntalla; E Oken; K Panoutsopoulou; J Pararajasingham; A Rodriguez; RM Salem; S Sebert; N Siitonen; DP Strachan; YY Teo; B Valcarcel; G Willemsen; E Zeggini; DI Boomsma; C Cooper; M Gillman; B Hocher; TA Lakka; KL Mohlke; GV Dedoussis; KK Ong; ER Pearson; TS Price; C Power; OT Raitakari; SM Saw; A Scherag; O Simell; TIA Sorensen; JF Wilson

doi:10.1038/ng.2245

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

Arfan Ikram, M Fornage, AV Smith, S Seshadri, R Schmidt, S Debette, Henri Vrooman, S Sigurdsson, S Ropele, Rob Taal, Dennis Mook, LH Coker, WT Longstreth, Wiro Niessen, AL DeStefano, A Beiser, AP Zijdenbos, M Struchalin, CR Jack, Fernando RivadeneiraAndré Uitterlinden, DS Knopman, AL Hartikainen, CE Pennell, E Thiering, Eric Steegers, H Hakonarson, J (Joachim) Heinrich, LJ Palmer, MR Jarvelin, MI McCarthy, SFA Grant, B St Pourcain, NJ Timpson, GD Smith, U Sovio, MA Nalls, R (Rhoda) Au, Bert Hofman, H Gudnason, Aad van der Lugt, TB Harris, WM Meeks, Meike Vernooij, MA van Buchem, D Catellier, Vincent Jaddoe, V Gudnason, BG Windham, PA Wolf, Cornelia Duijn, TH Mosley, Heléna Schmidt, LJ (Lenore) Launer, Monique Breteler, C DeCarli, LS Adair, W Ang, M Atalay, T vanBeijsterveldt, N Bergen, K Benke, D Berry, L Coin, OSP Davis, P Elliott, C Flexeder, T Frayling, Romy Gaillard, M Groen-Blokhuis, LK Goh, CMA Haworth, D Hadley, J Hedebrand, A Hinney, JN Hirschhorn, JW Holloway, C Holst, JJ (Jouke Jan) Hottenga, M Horikoshi, V Huikari, E Hypponen, TO Kilpelainen, M Kirin, M Kowgier, HM Lakka, LA Lange, DA Lawlor, T Lehtimaki, A Lewin, C Lindgren, V Lindi, R Maggi, J Marsh, C Middeldorp, I Millwood, JC Murray, M Nivard, EA Nohr, I Ntalla, E Oken, K Panoutsopoulou, J Pararajasingham, A Rodriguez, RM Salem, S Sebert, N Siitonen, DP Strachan, YY Teo, B Valcarcel, G Willemsen, E Zeggini, DI Boomsma, C Cooper, M Gillman, B Hocher, TA Lakka, KL Mohlke, GV Dedoussis, KK Ong, ER Pearson, TS Price, C Power, OT Raitakari, SM Saw, A Scherag, O Simell, TIA Sorensen, JF Wilson

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

99 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 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	Undefined/Unknown
Pages (from-to)	539-+
Journal	Nature Genetics
Volume	44
Issue number	5
DOIs	https://doi.org/10.1038/ng.2245
Publication status	Published - 2012

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Access to Document

10.1038/ng.2245

http://hdl.handle.net/1765/55973

Cite this

Ikram, A., Fornage, M., Smith, AV., Seshadri, S., Schmidt, R., Debette, S., Vrooman, H., Sigurdsson, S., Ropele, S., Taal, R., Mook, D., Coker, LH., Longstreth, WT., Niessen, W., DeStefano, AL., Beiser, A., Zijdenbos, AP., Struchalin, M., Jack, CR., ... Wilson, JF. (2012). Common variants at 6q22 and 17q21 are associated with intracranial volume. Nature Genetics, 44(5), 539-+. https://doi.org/10.1038/ng.2245

@article{30b3646fea8c4beeb9ecba606a79fce4,

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.",

author = "Arfan Ikram and M Fornage and AV Smith and S Seshadri and R Schmidt and S Debette and Henri Vrooman and S Sigurdsson and S Ropele and Rob Taal and Dennis Mook and LH Coker and WT Longstreth and Wiro Niessen and AL DeStefano and A Beiser and AP Zijdenbos and M Struchalin and CR Jack and Fernando Rivadeneira and Andr{\'e} Uitterlinden and DS Knopman and AL Hartikainen and CE Pennell and E Thiering and Eric Steegers and H Hakonarson and Heinrich, {J (Joachim)} and LJ Palmer and MR Jarvelin and MI McCarthy and SFA Grant and {St Pourcain}, B and NJ Timpson and GD Smith and U Sovio and MA Nalls and Au, {R (Rhoda)} and Bert Hofman and H Gudnason and {van der Lugt}, Aad and TB Harris and WM Meeks and Meike Vernooij and {van Buchem}, MA and D Catellier and Vincent Jaddoe and V Gudnason and BG Windham and PA Wolf and Cornelia Duijn and TH Mosley and Hel{\'e}na Schmidt and Launer, {LJ (Lenore)} and Monique Breteler and C DeCarli and LS Adair and W Ang and M Atalay and T vanBeijsterveldt and N Bergen and K Benke and D Berry and L Coin and OSP Davis and P Elliott and C Flexeder and T Frayling and Romy Gaillard and M Groen-Blokhuis and LK Goh and CMA Haworth and D Hadley and J Hedebrand and A Hinney and JN Hirschhorn and JW Holloway and C Holst and Hottenga, {JJ (Jouke Jan)} and M Horikoshi and V Huikari and E Hypponen and TO Kilpelainen and M Kirin and M Kowgier and HM Lakka and LA Lange and DA Lawlor and T Lehtimaki and A Lewin and C Lindgren and V Lindi and R Maggi and J Marsh and C Middeldorp and I Millwood and JC Murray and M Nivard and EA Nohr and I Ntalla and E Oken and K Panoutsopoulou and J Pararajasingham and A Rodriguez and RM Salem and S Sebert and N Siitonen and DP Strachan and YY Teo and B Valcarcel and G Willemsen and E Zeggini and DI Boomsma and C Cooper and M Gillman and B Hocher and TA Lakka and KL Mohlke and GV Dedoussis and KK Ong and ER Pearson and TS Price and C Power and OT Raitakari and SM Saw and A Scherag and O Simell and TIA Sorensen and JF Wilson",

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volume = "44",

pages = "539--+",

journal = "Nature Genetics",

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Ikram, A, Fornage, M, Smith, AV, Seshadri, S, Schmidt, R, Debette, S, Vrooman, H, Sigurdsson, S, Ropele, S, Taal, R, Mook, D, Coker, LH, Longstreth, WT, Niessen, W, DeStefano, AL, Beiser, A, Zijdenbos, AP, Struchalin, M, Jack, CR, Rivadeneira, F , Uitterlinden, A, Knopman, DS, Hartikainen, AL, Pennell, CE, Thiering, E, Steegers, E, Hakonarson, H, Heinrich, J, Palmer, LJ, Jarvelin, MR, McCarthy, MI, Grant, SFA, St Pourcain, B, Timpson, NJ, Smith, GD, Sovio, U, Nalls, MA, Au, R, Hofman, B, Gudnason, H, van der Lugt, A, Harris, TB, Meeks, WM, Vernooij, M, van Buchem, MA, Catellier, D, Jaddoe, V, Gudnason, V, Windham, BG, Wolf, PA, Duijn, C, Mosley, TH, Schmidt, H, Launer, LJ, Breteler, M, DeCarli, C, Adair, LS, Ang, W, Atalay, M, vanBeijsterveldt, T, Bergen, N, Benke, K, Berry, D, Coin, L, Davis, OSP, Elliott, P, Flexeder, C, Frayling, T, Gaillard, R, Groen-Blokhuis, M, Goh, LK, Haworth, CMA, Hadley, D, Hedebrand, J, Hinney, A, Hirschhorn, JN, Holloway, JW, Holst, C, Hottenga, JJ, Horikoshi, M, Huikari, V, Hypponen, E, Kilpelainen, TO, Kirin, M, Kowgier, M, Lakka, HM, Lange, LA, Lawlor, DA, Lehtimaki, T, Lewin, A, Lindgren, C, Lindi, V, Maggi, R, Marsh, J, Middeldorp, C, Millwood, I, Murray, JC, Nivard, M, Nohr, EA, Ntalla, I, Oken, E, Panoutsopoulou, K, Pararajasingham, J, Rodriguez, A, Salem, RM, Sebert, S, Siitonen, N, Strachan, DP, Teo, YY, Valcarcel, B, Willemsen, G, Zeggini, E, Boomsma, DI, Cooper, C, Gillman, M, Hocher, B, Lakka, TA, Mohlke, KL, Dedoussis, GV, Ong, KK, Pearson, ER, Price, TS, Power, C, Raitakari, OT, Saw, SM, Scherag, A, Simell, O, Sorensen, TIA & Wilson, JF 2012, 'Common variants at 6q22 and 17q21 are associated with intracranial volume', Nature Genetics, vol. 44, no. 5, pp. 539-+. https://doi.org/10.1038/ng.2245

TY - JOUR

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

AU - Ikram, Arfan

AU - Fornage, M

AU - Smith, AV

AU - Seshadri, S

AU - Schmidt, R

AU - Debette, S

AU - Vrooman, Henri

AU - Sigurdsson, S

AU - Ropele, S

AU - Taal, Rob

AU - Mook, Dennis

AU - Coker, LH

AU - Longstreth, WT

AU - Niessen, Wiro

AU - DeStefano, AL

AU - Beiser, A

AU - Zijdenbos, AP

AU - Struchalin, M

AU - Jack, CR

AU - Rivadeneira, Fernando

AU - Uitterlinden, André

AU - Knopman, DS

AU - Hartikainen, AL

AU - Pennell, CE

AU - Thiering, E

AU - Steegers, Eric

AU - Hakonarson, H

AU - Heinrich, J (Joachim)

AU - Palmer, LJ

AU - Jarvelin, MR

AU - McCarthy, MI

AU - Grant, SFA

AU - St Pourcain, B

AU - Timpson, NJ

AU - Smith, GD

AU - Sovio, U

AU - Nalls, MA

AU - Au, R (Rhoda)

AU - Hofman, Bert

AU - Gudnason, H

AU - van der Lugt, Aad

AU - Harris, TB

AU - Meeks, WM

AU - Vernooij, Meike

AU - van Buchem, MA

AU - Catellier, D

AU - Jaddoe, Vincent

AU - Gudnason, V

AU - Windham, BG

AU - Wolf, PA

AU - Duijn, Cornelia

AU - Mosley, TH

AU - Schmidt, Heléna

AU - Launer, LJ (Lenore)

AU - Breteler, Monique

AU - DeCarli, C

AU - Adair, LS

AU - Ang, W

AU - Atalay, M

AU - vanBeijsterveldt, T

AU - Bergen, N

AU - Benke, K

AU - Berry, D

AU - Coin, L

AU - Davis, OSP

AU - Elliott, P

AU - Flexeder, C

AU - Frayling, T

AU - Gaillard, Romy

AU - Groen-Blokhuis, M

AU - Goh, LK

AU - Haworth, CMA

AU - Hadley, D

AU - Hedebrand, J

AU - Hinney, A

AU - Hirschhorn, JN

AU - Holloway, JW

AU - Holst, C

AU - Hottenga, JJ (Jouke Jan)

AU - Horikoshi, M

AU - Huikari, V

AU - Hypponen, E

AU - Kilpelainen, TO

AU - Kirin, M

AU - Kowgier, M

AU - Lakka, HM

AU - Lange, LA

AU - Lawlor, DA

AU - Lehtimaki, T

AU - Lewin, A

AU - Lindgren, C

AU - Lindi, V

AU - Maggi, R

AU - Marsh, J

AU - Middeldorp, C

AU - Millwood, I

AU - Murray, JC

AU - Nivard, M

AU - Nohr, EA

AU - Ntalla, I

AU - Oken, E

AU - Panoutsopoulou, K

AU - Pararajasingham, J

AU - Rodriguez, A

AU - Salem, RM

AU - Sebert, S

AU - Siitonen, N

AU - Strachan, DP

AU - Teo, YY

AU - Valcarcel, B

AU - Willemsen, G

AU - Zeggini, E

AU - Boomsma, DI

AU - Cooper, C

AU - Gillman, M

AU - Hocher, B

AU - Lakka, TA

AU - Mohlke, KL

AU - Dedoussis, GV

AU - Ong, KK

AU - Pearson, ER

AU - Price, TS

AU - Power, C

AU - Raitakari, OT

AU - Saw, SM

AU - Scherag, A

AU - Simell, O

AU - Sorensen, TIA

AU - Wilson, JF

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 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.

U2 - 10.1038/ng.2245

DO - 10.1038/ng.2245

M3 - Article

C2 - 22504418

SN - 1061-4036

VL - 44

SP - 539-+

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -