Novel genetic loci associated with hippocampal volume

被引：212

作者：

Hibar, Derrek P. ^{[1
]}

Adams, Hieab H. H. ^{[2
,3
]}

Jahanshad, Neda ^{[1
]}

Chauhan, Ganesh ^{[4
]}

Stein, Jason L. ^{[1
,5
,6
]}

Hofer, Edith ^{[7
,8
]}

Renteria, Miguel E. ^{[9
]}

Bis, Joshua C. ^{[10
]}

Arias-Vasquez, Alejandro ^{[11
,12
,13
,14
]}

Ikram, M. Kamran ^{[2
,15
,16
,17
,18
]}

Desrivieres, Sylvane ^{[19
]}

Vernooij, Meike W. ^{[2
,3
]}

Abramovic, Lucija ^{[20
]}

Alhusaini, Saud ^{[21
,22
]}

Amin, Najaf ^{[2
]}

Andersson, Micael ^{[23
,24
]}

Arfanakis, Konstantinos ^{[25
,26
,27
]}

Aribisala, Benjamin S. ^{[28
,29
,30
]}

Armstrong, Nicola J. ^{[31
,32
]}

Athanasiu, Lavinia ^{[33
,34
]}

Axelsson, Tomas ^{[35
]}

Beecham, Ashley H. ^{[36
,37
]}

Beiser, Alexa ^{[38
,39
,40
]}

Bernard, Manon ^{[41
]}

Blanton, Susan H. ^{[36
,37
]}

Bohlken, Marc M. ^{[20
]}

Boks, Marco P. ^{[20
]}

Bralten, Janita ^{[11
,14
]}

Brickman, Adam M. ^{[42
,43
,44
]}

Carmichael, Owen ^{[45
]}

Chakravarty, M. Mallar ^{[46
,47
]}

Chen, Qiang ^{[48
]}

Ching, Christopher R. K. ^{[1
,49
]}

Chouraki, Vincent ^{[38
,40
,50
]}

Cuellar-Partida, Gabriel ^{[9
]}

Crivello, Fabrice ^{[51
]}

Den Braber, Anouk ^{[52
,53
]}

Nhat Trung Doan ^{[33
]}

Ehrlich, Stefan ^{[54
,55
,56
]}

Giddaluru, Sudheer ^{[57
,58
]}

Goldman, Aaron L. ^{[48
]}

Gottesman, Rebecca F. ^{[59
]}

Grimm, Oliver ^{[60
]}

Griswold, Michael E. ^{[61
]}

Guadalupe, Tulio ^{[62
,63
]}

Gutman, Boris A. ^{[1
]}

Hass, Johanna ^{[64
]}

Haukvik, Unn K. ^{[33
,65
]}

Hoehn, David ^{[66
]}

Holmes, Avram J. ^{[55
,67
]}

机构：

[1] Univ Southern Calif, Imaging Genet Ctr, USC Mark & Mary Stevens Neuroimaging & Informat I, Keck Sch Med, Marina Del Rey, CA 90292 USA

[2] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3015 CE Rotterdam, Netherlands

[3] Erasmus MC, Dept Radiol & Nucl Med, NL-3015 CE Rotterdam, Netherlands

[4] Univ Bordeaux, INSERM Unit U1219, F-33076 Bordeaux, France

[5] UNC, Dept Genet, Chapel Hill, NC 27599 USA

[6] UNC, UNC Neurosci Ctr, Chapel Hill, NC 27599 USA

[7] Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Auenbruggerpl 22, A-8036 Graz, Austria

[8] Med Univ Graz, Inst Med Informat Stat & Documentat, Auenbruggerpl 22, A-8036 Graz, Austria

[9] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia

[10] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, 1730 Minor Ave Suite 1360, Seattle, WA 98101 USA

[11] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 GA Nijmegen, Netherlands

[12] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6525 GA Nijmegen, Netherlands

[13] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6525 GA Nijmegen, Netherlands

[14] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 GA Nijmegen, Netherlands

[15] Duke NUS Grad Med Sch, Acad Med Res Inst, Singapore 169857, Singapore

[16] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore

[17] Natl Univ Hlth Syst, MACC, Singapore 119228, Singapore

[18] Natl Univ Singapore, Dept Pharmacol, Singapore 119077, Singapore

[19] Kings Coll London, MRC SGDP Ctr, Inst Psychiat Psychol & Neurosci, London SE5 8AF, England

[20] UMC Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CX Utrecht, Netherlands

[21] McGill Univ, Dept Neurol & Neurosurg, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada

[22] Royal Coll Surgeons Ireland, 123 St Stephens Green, Dublin 2, Ireland

[23] Umea Univ, Dept Integrat Med Biol, S-90187 Umea, Sweden

[24] Umea Univ, Umea Ctr Funct Brain Imaging, S-90187 Umea, Sweden

[25] IIT, Dept Biomed Engn, Chicago, IL 60612 USA

[26] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA

[27] Rush Univ, Med Ctr, Dept Diagnost Radiol & Nucl Med, Chicago, IL 60616 USA

[28] Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh EH4 2XU, Midlothian, Scotland

[29] Lagos State Univ, Dept Comp Sci, PMB 01 LASU, Lagos, Nigeria

[30] Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Platform Sci Excellence SINAPSE Collaborat, Edinburgh EH16 4SB, Midlothian, Scotland

[31] Univ New South Wales, Ctr Healthy Brain Ageing, Sch Psychiat, Sydney, NSW 2052, Australia

[32] Murdoch Univ, Math & Stat, Perth, WA 6150, Australia

[33] Univ Oslo, NORMENT KG Jebsen Ctr, Inst Clin Med, N-0315 Oslo, Norway

[34] Oslo Univ Hosp, NORMENT KG Jebsen Ctr, Div Mental Hlth & Addict, N-0424 Oslo, Norway

[35] Uppsala Univ, Dept Med Sci Mol Med & Sci Life Lab, Box 1432, SE-75144 Uppsala, Sweden

[36] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn Dept Human Genet, Miami, FL 33136 USA

[37] Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL 33136 USA

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

[39] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA

[40] Framingham Heart Dis Epidemiol Study, 17 Mt Wayte Ave, Framingham, MA 01703 USA

[41] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada

[42] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, 639 West 1168th St, New York, NY 10032 USA

[43] Columbia Univ, Med Ctr, GH Sergievsky Ctr, 639 West 1168th St, New York, NY 10032 USA

[44] Columbia Univ, Med Ctr, Dept Neurol, 639 West 1168th St, New York, NY 10032 USA

[45] Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA

[46] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Montreal, PQ H4H 1R3, Canada

[47] McGill Univ, Dept Psychiat & Biomed Engn, Montreal, PQ H3A 2B4, Canada

[48] Lieber Inst Brain Dev, Baltimore, MD 21205 USA

[49] Univ Calif Los Angeles, Sch Med, Interdept Neurosci Grad Program, Los Angeles, CA 90095 USA

[50] Univ Lille, CHU Lille, INSERM, Inst Pasteur Lille,RID AGE Risk Factors & Mol Det, F-59000 Lille, France

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; TEMPORAL-LOBE EPILEPSY; SUSCEPTIBILITY LOCI; ALZHEIMERS-DISEASE; BIPOLAR DISORDER; COMMON VARIANTS; BRAIN-REGIONS; MEMORY; SUBFIELDS; METAANALYSIS;

D O I：

10.1038/ncomms13624

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

引用

页数：12

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