Common variants at 6q22 and 17q21 are associated with intracranial volume. / 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.; 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.; St Pourcain, Beate; 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; vanBeijsterveldt, 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; Hottenga, Jouke Jan; Horikoshi, Momoko; Huikari, Ville; Hypponen, Elina; Kilpelainen, Tuomas O.; Kirin, Mirna; Kowgier, Matthew; Lakka, Hanna-Maaria; Lange, Leslie A.; Lawlor, Debbie A.; Lehtimaki, 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; Valcarcel, 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; Sorensen, Thorkild I. A.; Wilson, James F.; Early Growth Genetics EGG Consorti, Cohorts Heart Aging Res Genomic Ep.
In: Nature Genetics, Vol. 44, No. 5, 05.2012, p. 539-544.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Common variants at 6q22 and 17q21 are associated with intracranial volume
A1 - Ikram,M. Arfan
A1 - Fornage,Myriam
A1 - Smith,Albert V.
A1 - Seshadri,Sudha
A1 - Schmidt,Reinhold
A1 - Debette,Stephanie
A1 - Vrooman,Henri A.
A1 - Sigurdsson,Sigurdur
A1 - Ropele,Stefan
A1 - Taal,H. Rob
A1 - Mook-Kanamori,Dennis O.
A1 - Coker,Laura H.
A1 - Longstreth,W. T.
A1 - Niessen,Wiro J.
A1 - DeStefano,Anita L.
A1 - Beiser,Alexa
A1 - Zijdenbos,Alex P.
A1 - Struchalin,Maksim
A1 - Jack,Clifford R.
A1 - Rivadeneira,Fernando
A1 - Uitterlinden,Andre G.
A1 - Knopman,David S.
A1 - Hartikainen,Anna-Liisa
A1 - Pennell,Craig E.
A1 - Thiering,Elisabeth
A1 - Steegers,Eric A. P.
A1 - Hakonarson,Hakon
A1 - Heinrich,Joachim
A1 - Palmer,Lyle J.
A1 - Jarvelin,Marjo-Riitta
A1 - McCarthy,Mark I.
A1 - Grant,Struan F. A.
A1 - St Pourcain,Beate
A1 - Timpson,Nicholas J.
A1 - Smith,George Davey
A1 - Sovio,Ulla
A1 - Nalls,Mike A.
A1 - Au,Rhoda
A1 - Hofman,Albert
A1 - Gudnason,Haukur
A1 - van der Lugt,Aad
A1 - Harris,Tamara B.
A1 - Meeks,William M.
A1 - Vernooij,Meike W.
A1 - van Buchem,Mark A.
A1 - Catellier,Diane
A1 - Jaddoe,Vincent W. V.
A1 - Gudnason,Vilmundur
A1 - Windham,B. Gwen
A1 - Wolf,Philip A.
A1 - van Duijn,Cornelia M.
A1 - Mosley,Thomas H.
A1 - Schmidt,Helena
A1 - Launer,Lenore J.
A1 - Breteler,Monique M. B.
A1 - DeCarli,Charles
A1 - Adair,Linda S.
A1 - Ang,Wei
A1 - Atalay,Mustafa
A1 - vanBeijsterveldt,Toos
A1 - Bergen,Nienke
A1 - Benke,Kelly
A1 - Berry,Diane
A1 - Coin,Lachlan
A1 - Davis,Oliver S. P.
A1 - Elliott,Paul
A1 - Flexeder,Claudia
A1 - Frayling,Tim
A1 - Gaillard,Romy
A1 - Groen-Blokhuis,Maria
A1 - Goh,Liang-Kee
A1 - Haworth,Claire M. A.
A1 - Hadley,Dexter
A1 - Hedebrand,Johannes
A1 - Hinney,Anke
A1 - Hirschhorn,Joel N.
A1 - Holloway,John W.
A1 - Holst,Claus
A1 - Hottenga,Jouke Jan
A1 - Horikoshi,Momoko
A1 - Huikari,Ville
A1 - Hypponen,Elina
A1 - Kilpelainen,Tuomas O.
A1 - Kirin,Mirna
A1 - Kowgier,Matthew
A1 - Lakka,Hanna-Maaria
A1 - Lange,Leslie A.
A1 - Lawlor,Debbie A.
A1 - Lehtimaki,Terho
A1 - Lewin,Alex
A1 - Lindgren,Cecilia
A1 - Lindi,Virpi
A1 - Maggi,Reedik
A1 - Marsh,Julie
A1 - Middeldorp,Christel
A1 - Millwood,Iona
A1 - Murray,Jeffrey C.
A1 - Nivard,Michel
A1 - Nohr,Ellen Aagaard
A1 - Ntalla,Ioanna
A1 - Oken,Emily
A1 - Panoutsopoulou,Kalliope
A1 - Pararajasingham,Jennifer
A1 - Rodriguez,Alina
A1 - Salem,Rany M.
A1 - Sebert,Sylvain
A1 - Siitonen,Niina
A1 - Strachan,David P.
A1 - Teo,Yik-Ying
A1 - Valcarcel,Beatriz
A1 - Willemsen,Gonneke
A1 - Zeggini,Eleftheria
A1 - Boomsma,Dorret I.
A1 - Cooper,Cyrus
A1 - Gillman,Matthew
A1 - Hocher,Berthold
A1 - Lakka,Timo A.
A1 - Mohlke,Karen L.
A1 - Dedoussis,George V.
A1 - Ong,Ken K.
A1 - Pearson,Ewan R.
A1 - Price,Thomas S.
A1 - Power,Chris
A1 - Raitakari,Olli T.
A1 - Saw,Seang-Mei
A1 - Scherag,Andre
A1 - Simell,Olli
A1 - Sorensen,Thorkild I. A.
A1 - Wilson,James F.
A1 - Early Growth Genetics EGG Consorti, Cohorts Heart Aging Res Genomic Ep
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 - Jaddoe,Vincent W. V.
AU - Gudnason,Vilmundur
AU - Windham,B. Gwen
AU - Wolf,Philip A.
AU - van Duijn,Cornelia M.
AU - Mosley,Thomas H.
AU - Schmidt,Helena
AU - Launer,Lenore J.
AU - Breteler,Monique M. B.
AU - DeCarli,Charles
AU - Adair,Linda S.
AU - Ang,Wei
AU - Atalay,Mustafa
AU - vanBeijsterveldt,Toos
AU - Bergen,Nienke
AU - Benke,Kelly
AU - Berry,Diane
AU - Coin,Lachlan
AU - Davis,Oliver S. P.
AU - Elliott,Paul
AU - Flexeder,Claudia
AU - Frayling,Tim
AU - Gaillard,Romy
AU - Groen-Blokhuis,Maria
AU - Goh,Liang-Kee
AU - Haworth,Claire M. A.
AU - Hadley,Dexter
AU - Hedebrand,Johannes
AU - Hinney,Anke
AU - Hirschhorn,Joel N.
AU - Holloway,John W.
AU - Holst,Claus
AU - Hottenga,Jouke Jan
AU - Horikoshi,Momoko
AU - Huikari,Ville
AU - Hypponen,Elina
AU - Kilpelainen,Tuomas O.
AU - Kirin,Mirna
AU - Kowgier,Matthew
AU - Lakka,Hanna-Maaria
AU - Lange,Leslie A.
AU - Lawlor,Debbie A.
AU - Lehtimaki,Terho
AU - Lewin,Alex
AU - Lindgren,Cecilia
AU - Lindi,Virpi
AU - Maggi,Reedik
AU - Marsh,Julie
AU - Middeldorp,Christel
AU - Millwood,Iona
AU - Murray,Jeffrey C.
AU - Nivard,Michel
AU - Nohr,Ellen Aagaard
AU - Ntalla,Ioanna
AU - Oken,Emily
AU - Panoutsopoulou,Kalliope
AU - Pararajasingham,Jennifer
AU - Rodriguez,Alina
AU - Salem,Rany M.
AU - Sebert,Sylvain
AU - Siitonen,Niina
AU - Strachan,David P.
AU - Teo,Yik-Ying
AU - Valcarcel,Beatriz
AU - Willemsen,Gonneke
AU - Zeggini,Eleftheria
AU - Boomsma,Dorret I.
AU - Cooper,Cyrus
AU - Gillman,Matthew
AU - Hocher,Berthold
AU - Lakka,Timo A.
AU - Mohlke,Karen L.
AU - Dedoussis,George V.
AU - Ong,Ken K.
AU - Pearson,Ewan R.
AU - Price,Thomas S.
AU - Power,Chris
AU - Raitakari,Olli T.
AU - Saw,Seang-Mei
AU - Scherag,Andre
AU - Simell,Olli
AU - Sorensen,Thorkild I. A.
AU - Wilson,James F.
AU - Early Growth Genetics EGG Consorti, 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 &lt; 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.</p>
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 &lt; 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.</p>
U2 - 10.1038/ng.2245
DO - 10.1038/ng.2245
M1 - Article
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 5
VL - 44
SP - 539
EP - 544
ER -