Identification of common variants associated with human hippocampal and intracranial volumes

the Alzheimer's Disease Neuroimaging Initiative (ADNI); Jason L Stein; Sarah E Medland; Alejandro Arias Vasquez; Derrek P Hibar; Rudy E Senstad; Anderson M Winkler; Roberto Toro; Katja Appel; Richard Bartecek; Orjan Bergmann; Manon Bernard; Andrew A Brown; Dara M Cannon; M Mallar Chakravarty; Andrea Christoforou; Martin Domin; Oliver Grimm; Marisa Hollinshead; Avram J Holmes; Georg Homuth; Jouke-Jan Hottenga; Camilla Langan; Lorna M Lopez; Narelle K Hansell; Kristy S Hwang; Sungeun Kim; Gonzalo Laje; Phil H Lee; Xinmin Liu; Eva Loth; Anbarasu Lourdusamy; Morten Mattingsdal; Sebastian Mohnke; Susana Muñoz Maniega; Kwangsik Nho; Allison C Nugent; Gail Davies; Stephen M Lawrie; David C Liewald; Natalie A Royle; Colin Smith; Maria C Valdés Hernández; Jeremy Hall; David J Porteous; John M Starr; Jessika Sussmann; Mark E Bastin; Ian J Deary; Andrew M McIntosh; Joanna M Wardlaw

doi:10.1038/ng.2250

Identification of common variants associated with human hippocampal and intracranial volumes

the Alzheimer's Disease Neuroimaging Initiative (ADNI), Jason L Stein, Sarah E Medland, Alejandro Arias Vasquez, Derrek P Hibar, Rudy E Senstad, Anderson M Winkler, Roberto Toro, Katja Appel, Richard Bartecek, Orjan Bergmann, Manon Bernard, Andrew A Brown, Dara M Cannon, M Mallar Chakravarty, Andrea Christoforou, Martin Domin, Oliver Grimm, Marisa Hollinshead, Avram J HolmesGeorg Homuth, Jouke-Jan Hottenga, Camilla Langan, Lorna M Lopez, Narelle K Hansell, Kristy S Hwang, Sungeun Kim, Gonzalo Laje, Phil H Lee, Xinmin Liu, Eva Loth, Anbarasu Lourdusamy, Morten Mattingsdal, Sebastian Mohnke, Susana Muñoz Maniega, Kwangsik Nho, Allison C Nugent, Gail Davies, Stephen M Lawrie, David C Liewald, Natalie A Royle, Colin Smith, Maria C Valdés Hernández, Jeremy Hall, David J Porteous, John M Starr, Jessika Sussmann, Mark E Bastin, Ian J Deary, Andrew M McIntosh, Joanna M Wardlaw

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

Abstract

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)).

Original language	English
Pages (from-to)	552-561
Number of pages	10
Journal	Nature Genetics
Volume	44
Issue number	5
Early online date	15 Apr 2012
DOIs	https://doi.org/10.1038/ng.2250
Publication status	Published - 2012

Access to Document

10.1038/ng.2250

Identification of common variants associated with human hippocampal and intracranial volumes
© 2012 Nature America, Inc. All rights reserved.
Accepted author manuscript, 2.1 MB

http://www.nature.com/ng/journal/v44/n5/full/ng.2250.html

Cite this

the Alzheimer's Disease Neuroimaging Initiative (ADNI), Stein, J. L., Medland, S. E., Vasquez, A. A., Hibar, D. P., Senstad, R. E., Winkler, A. M., Toro, R., Appel, K., Bartecek, R., Bergmann, O., Bernard, M., Brown, A. A., Cannon, D. M., Chakravarty, M. M., Christoforou, A., Domin, M., Grimm, O., Hollinshead, M., ... Wardlaw, J. M. (2012). Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics, 44(5), 552-561. https://doi.org/10.1038/ng.2250

the Alzheimer's Disease Neuroimaging Initiative (ADNI) ; Stein, Jason L ; Medland, Sarah E ; Vasquez, Alejandro Arias ; Hibar, Derrek P ; Senstad, Rudy E ; Winkler, Anderson M ; Toro, Roberto ; Appel, Katja ; Bartecek, Richard ; Bergmann, Orjan ; Bernard, Manon ; Brown, Andrew A ; Cannon, Dara M ; Chakravarty, M Mallar ; Christoforou, Andrea ; Domin, Martin ; Grimm, Oliver ; Hollinshead, Marisa ; Holmes, Avram J ; Homuth, Georg ; Hottenga, Jouke-Jan ; Langan, Camilla ; Lopez, Lorna M ; Hansell, Narelle K ; Hwang, Kristy S ; Kim, Sungeun ; Laje, Gonzalo ; Lee, Phil H ; Liu, Xinmin ; Loth, Eva ; Lourdusamy, Anbarasu ; Mattingsdal, Morten ; Mohnke, Sebastian ; Maniega, Susana Muñoz ; Nho, Kwangsik ; Nugent, Allison C ; Davies, Gail ; Lawrie, Stephen M ; Liewald, David C ; Royle, Natalie A ; Smith, Colin ; Valdés Hernández, Maria C ; Hall, Jeremy ; Porteous, David J ; Starr, John M ; Sussmann, Jessika ; Bastin, Mark E ; Deary, Ian J ; McIntosh, Andrew M ; Wardlaw, Joanna M. / Identification of common variants associated with human hippocampal and intracranial volumes. In: Nature Genetics. 2012 ; Vol. 44, No. 5. pp. 552-561.

@article{db1b030a3c4b4cf297506988d7461d52,

title = "Identification of common variants associated with human hippocampal and intracranial volumes",

abstract = "Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)).",

author = "{the Alzheimer's Disease Neuroimaging Initiative (ADNI)} and Stein, {Jason L} and Medland, {Sarah E} and Vasquez, {Alejandro Arias} and Hibar, {Derrek P} and Senstad, {Rudy E} and Winkler, {Anderson M} and Roberto Toro and Katja Appel and Richard Bartecek and Orjan Bergmann and Manon Bernard and Brown, {Andrew A} and Cannon, {Dara M} and Chakravarty, {M Mallar} and Andrea Christoforou and Martin Domin and Oliver Grimm and Marisa Hollinshead and Holmes, {Avram J} and Georg Homuth and Jouke-Jan Hottenga and Camilla Langan and Lopez, {Lorna M} and Hansell, {Narelle K} and Hwang, {Kristy S} and Sungeun Kim and Gonzalo Laje and Lee, {Phil H} and Xinmin Liu and Eva Loth and Anbarasu Lourdusamy and Morten Mattingsdal and Sebastian Mohnke and Maniega, {Susana Mu{\~n}oz} and Kwangsik Nho and Nugent, {Allison C} and Gail Davies and Lawrie, {Stephen M} and Liewald, {David C} and Royle, {Natalie A} and Colin Smith and {Vald{\'e}s Hern{\'a}ndez}, {Maria C} and Jeremy Hall and Porteous, {David J} and Starr, {John M} and Jessika Sussmann and Bastin, {Mark E} and Deary, {Ian J} and McIntosh, {Andrew M} and Wardlaw, {Joanna M}",

year = "2012",

doi = "10.1038/ng.2250",

language = "English",

volume = "44",

pages = "552--561",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "5",

}

the Alzheimer's Disease Neuroimaging Initiative (ADNI), Stein, JL, Medland, SE, Vasquez, AA, Hibar, DP, Senstad, RE, Winkler, AM, Toro, R, Appel, K, Bartecek, R, Bergmann, O, Bernard, M, Brown, AA, Cannon, DM, Chakravarty, MM, Christoforou, A, Domin, M, Grimm, O, Hollinshead, M, Holmes, AJ, Homuth, G, Hottenga, J-J, Langan, C, Lopez, LM, Hansell, NK, Hwang, KS, Kim, S, Laje, G, Lee, PH, Liu, X, Loth, E, Lourdusamy, A, Mattingsdal, M, Mohnke, S, Maniega, SM, Nho, K, Nugent, AC, Davies, G , Lawrie, SM, Liewald, DC, Royle, NA, Smith, C , Valdés Hernández, MC, Hall, J, Porteous, DJ, Starr, JM, Sussmann, J, Bastin, ME , Deary, IJ , McIntosh, AM & Wardlaw, JM 2012, 'Identification of common variants associated with human hippocampal and intracranial volumes', Nature Genetics, vol. 44, no. 5, pp. 552-561. https://doi.org/10.1038/ng.2250

Identification of common variants associated with human hippocampal and intracranial volumes. / the Alzheimer's Disease Neuroimaging Initiative (ADNI); Stein, Jason L; Medland, Sarah E; Vasquez, Alejandro Arias; Hibar, Derrek P; Senstad, Rudy E; Winkler, Anderson M; Toro, Roberto; Appel, Katja; Bartecek, Richard; Bergmann, Orjan; Bernard, Manon; Brown, Andrew A; Cannon, Dara M; Chakravarty, M Mallar; Christoforou, Andrea; Domin, Martin; Grimm, Oliver; Hollinshead, Marisa; Holmes, Avram J; Homuth, Georg; Hottenga, Jouke-Jan; Langan, Camilla; Lopez, Lorna M; Hansell, Narelle K; Hwang, Kristy S; Kim, Sungeun; Laje, Gonzalo; Lee, Phil H; Liu, Xinmin; Loth, Eva; Lourdusamy, Anbarasu; Mattingsdal, Morten; Mohnke, Sebastian; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Davies, Gail ; Lawrie, Stephen M; Liewald, David C; Royle, Natalie A; Smith, Colin ; Valdés Hernández, Maria C; Hall, Jeremy; Porteous, David J; Starr, John M; Sussmann, Jessika; Bastin, Mark E ; Deary, Ian J ; McIntosh, Andrew M ; Wardlaw, Joanna M.

In: Nature Genetics, Vol. 44, No. 5, 2012, p. 552-561.

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

TY - JOUR

T1 - Identification of common variants associated with human hippocampal and intracranial volumes

AU - the Alzheimer's Disease Neuroimaging Initiative (ADNI)

AU - Stein, Jason L

AU - Medland, Sarah E

AU - Vasquez, Alejandro Arias

AU - Hibar, Derrek P

AU - Senstad, Rudy E

AU - Winkler, Anderson M

AU - Toro, Roberto

AU - Appel, Katja

AU - Bartecek, Richard

AU - Bergmann, Orjan

AU - Bernard, Manon

AU - Brown, Andrew A

AU - Cannon, Dara M

AU - Chakravarty, M Mallar

AU - Christoforou, Andrea

AU - Domin, Martin

AU - Grimm, Oliver

AU - Hollinshead, Marisa

AU - Holmes, Avram J

AU - Homuth, Georg

AU - Hottenga, Jouke-Jan

AU - Langan, Camilla

AU - Lopez, Lorna M

AU - Hansell, Narelle K

AU - Hwang, Kristy S

AU - Kim, Sungeun

AU - Laje, Gonzalo

AU - Lee, Phil H

AU - Liu, Xinmin

AU - Loth, Eva

AU - Lourdusamy, Anbarasu

AU - Mattingsdal, Morten

AU - Mohnke, Sebastian

AU - Maniega, Susana Muñoz

AU - Nho, Kwangsik

AU - Nugent, Allison C

AU - Davies, Gail

AU - Lawrie, Stephen M

AU - Liewald, David C

AU - Royle, Natalie A

AU - Smith, Colin

AU - Valdés Hernández, Maria C

AU - Hall, Jeremy

AU - Porteous, David J

AU - Starr, John M

AU - Sussmann, Jessika

AU - Bastin, Mark E

AU - Deary, Ian J

AU - McIntosh, Andrew M

AU - Wardlaw, Joanna M

PY - 2012

Y1 - 2012

N2 - Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)).

AB - Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)).

UR - http://www.scopus.com/inward/record.url?scp=84860351742&partnerID=8YFLogxK

U2 - 10.1038/ng.2250

DO - 10.1038/ng.2250

M3 - Article

C2 - 22504417

VL - 44

SP - 552

EP - 561

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 5

ER -

Identification of common variants associated with human hippocampal and intracranial volumes

Abstract

Access to Document

Other files and links

Fingerprint

Brain White mater imaging and cognitive ageing in the Lothian Birth Cohort of 1936:II

Disconnected Mind [Phase 2]

A genome wide association study of non pathological cognitive ageing

Cite this

Identification of common variants associated with human hippocampal and intracranial volumes

Abstract

Access to Document

Other files and links

Fingerprint

Projects

Brain White mater imaging and cognitive ageing in the Lothian Birth Cohort of 1936:II

Disconnected Mind [Phase 2]

A genome wide association study of non pathological cognitive ageing

Cite this