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

被引：108

作者：

Ikram, M. Arfan ^{[1
,2
,3
]}

Fornage, Myriam ^{[4
,5
]}

Smith, Albert V. ^{[6
,7
]}

Seshadri, Sudha ^{[8
,9
,10
]}

Schmidt, Reinhold ^{[11
]}

Debette, Stephanie ^{[8
,9
,12
]}

Vrooman, Henri A. ^{[2
,13
]}

Sigurdsson, Sigurdur ^{[6
]}

Ropele, Stefan ^{[11
]}

Taal, H. Rob ^{[1
,14
,15
]}

Mook-Kanamori, Dennis O. ^{[1
,14
,15
,16
]}

Coker, Laura H. ^{[17
]}

Longstreth, W. T., Jr. ^{[18
]}

Niessen, Wiro J. ^{[2
,13
,19
]}

DeStefano, Anita L. ^{[8
,9
,10
]}

Beiser, Alexa ^{[8
,9
,10
]}

Zijdenbos, Alex P. ^{[20
]}

Struchalin, Maksim ^{[1
]}

Jack, Clifford R., Jr. ^{[21
]}

Rivadeneira, Fernando ^{[2
,22
]}

Uitterlinden, Andre G. ^{[2
,22
]}

Knopman, David S. ^{[23
]}

Hartikainen, Anna-Liisa ^{[24
]}

Pennell, Craig E. ^{[25
]}

Thiering, Elisabeth ^{[26
]}

Steegers, Eric A. P. ^{[27
]}

Hakonarson, Hakon ^{[28
,29
]}

Heinrich, Joachim ^{[25
]}

Palmer, Lyle J. ^{[30
]}

Jarvelin, Marjo-Riitta ^{[31
,32
,33
,34
]}

McCarthy, Mark I. ^{[35
,36
]}

Grant, Struan F. A. ^{[28
,29
]}

St Pourcain, Beate ^{[37
]}

Timpson, Nicholas J. ^{[37
]}

Smith, George Davey ^{[37
]}

Sovio, Ulla ^{[31
,38
]}

Nalls, Mike A. ^{[39
]}

Au, Rhoda ^{[8
,11
]}

Hofman, Albert ^{[13
]}

Gudnason, Haukur ^{[6
]}

van der Lugt, Aad ^{[2
]}

Harris, Tamara B. ^{[40
]}

Meeks, William M. ^{[41
,42
]}

Vernooij, Meike W. ^{[1
,2
]}

van Buchem, Mark A. ^{[43
]}

Catellier, Diane ^{[44
]}

Jaddoe, Vincent W. V. ^{[1
,14
,15
]}

Gudnason, Vilmundur ^{[6
,7
]}

Windham, B. Gwen ^{[41
,42
]}

Wolf, Philip A. ^{[8
,10
]}

机构：

[1] Univ Med Ctr, Erasmus Med Ctr, Dept Epidemiol, Rotterdam, Netherlands

[2] Univ Med Ctr, Erasmus Med Ctr, Dept Radiol, Rotterdam, Netherlands

[3] Netherlands Consortium Hlth Aging, Leiden, Netherlands

[4] Univ Texas Houston, Inst Mol Med, Houston Hlth Sci Ctr, Houston, TX USA

[5] Univ Texas Houston, Ctr Human Genet, Houston Hlth Sci Ctr, Houston, TX USA

[6] Iceland Heart Assoc, Kopavogur, Iceland

[7] Univ Iceland, Fac Med, Reykjavik, Iceland

[8] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[9] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[10] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA

[11] Med Univ Graz, Dept Neurol, Graz, Austria

[12] INSERM, U708, Paris, France

[13] Univ Med Ctr, Erasmus Med Ctr, Dept Med Informat, Rotterdam, Netherlands

[14] Univ Med Ctr, Erasmus Med Ctr, Dept Pediat, Rotterdam, Netherlands

[15] Univ Med Ctr, Erasmus Med Ctr, Generat Study R, Rotterdam, Netherlands

[16] Weill Cornell Med Coll Qatar, Dept Physiol & Biophys, Doha, Qatar

[17] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA

[18] Univ Washington, Dept Neurol & Epidemiol, Seattle, WA 98195 USA

[19] Delft Univ Technol, Fac Sci Appl, Delft, Netherlands

[20] Biospective Inc, Montreal, PQ, Canada

[21] Mayo Clin, Dept Radiol, Rochester, MN USA

[22] Univ Med Ctr, Erasmus Med Ctr, Dept Internal Med, Rotterdam, Netherlands

[23] Mayo Clin, Dept Neurol, Rochester, MN USA

[24] Univ Oulu, Dept Obstet & Gynecol, Inst Clin Med, SF-90220 Oulu, Finland

[25] Univ Western Australia, Sch Womens & Infants Hlth, Crawley, WA, Australia

[26] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany

[27] Univ Med Ctr, Erasmus Med Ctr, Dept Obstet & Gynaecol, Rotterdam, Netherlands

[28] Childrens Hosp Philadelphia, Ctr Appl Genom, Abramsom Res Ctr, Philadelphia, PA 19104 USA

[29] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA

[30] Univ Toronto, Ontario Inst Canc Res, Toronto, ON, Canada

[31] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, Sch Publ Hlth, MRC,HPA,Ctr Environm & Hlth,Fac Med, London, England

[32] Univ Oulu, Inst Hlth Sci, Oulu, Finland

[33] Univ Oulu, Bioctr Oulu, Oulu, Finland

[34] Natl Inst Hlth & Welf, Dept Children Young People & Families, Oulu, Finland

[35] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England

[36] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[37] Univ Bristol, MRC Ctr Causal Anal Translat Epidemiol, Sch Social & Community Med, Bristol, Avon, England

[38] London Sch Hyg & Trop Med, Dept Med Stat, London WC1, England

[39] NIA, Neurogenet Lab, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA

[40] NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA

[41] Univ Mississippi, Med Ctr, Dept Med Geriatr, Jackson, MS 39216 USA

[42] Univ Mississippi, Med Ctr, Dept Neurol, Jackson, MS 39216 USA

[43] Leiden Univ, Dept Radiol, Med Ctr, Leiden, Netherlands

[44] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA

[45] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria

[46] German Ctr Neurol Dis DZNE, Bonn, Germany

[47] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA

[48] Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA

[49] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA

[50] Univ Eastern Finland, Dept Physiol, Inst Biomed, Kuopio, Finland

来源：

NATURE GENETICS | 2012年 / 44卷 / 05期

基金：

英国医学研究理事会; 英国惠康基金; 加拿大健康研究院; 芬兰科学院;

关键词：

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

D O I：

10.1038/ng.2245

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：539 / +

页数：7

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