Manuel Mattheisen

Identification of common variants associated with human hippocampal and intracranial volumes

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Jason L Stein
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  • Sarah E Medland
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  • Alejandro Arias Vasquez
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  • Derrek P Hibar
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  • Rudy E Senstad
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  • Anderson M Winkler
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  • Roberto Toro
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  • Katja Appel
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  • Richard Bartecek
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  • Ørjan Bergmann
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  • Manon Bernard
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  • Andrew A Brown
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  • Dara M Cannon
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  • M Mallar Chakravarty
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  • Andrea Christoforou
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  • Martin Domin
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  • Oliver Grimm
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  • Marisa Hollinshead
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  • Avram J Holmes
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  • Georg Homuth
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  • Jouke-Jan Hottenga
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  • Camilla Langan
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  • Lorna M Lopez
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  • Narelle K Hansell
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  • Kristy S Hwang
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  • Sungeun Kim
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  • Gonzalo Laje
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  • Phil H Lee
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  • Xinmin Liu
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  • Eva Loth
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  • Anbarasu Lourdusamy
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  • Morten Mattingsdal
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  • Sebastian Mohnke
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  • Susana Muñoz Maniega
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  • Kwangsik Nho
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  • Allison C Nugent
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  • Carol O'Brien
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  • Martina Papmeyer
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  • Benno Pütz
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  • Adaikalavan Ramasamy
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  • Jerod Rasmussen
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  • Mark Rijpkema
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  • Shannon L Risacher
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  • J Cooper Roddey
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  • Emma J Rose
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  • Mina Ryten
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  • Li Shen
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  • Emma Sprooten
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  • Eric Strengman
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  • Manuel Mattheisen
  • Alzheimer's Disease Neuroimaging Initiative
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 languageEnglish
JournalNature Genetics
Volume44
Issue5
Pages (from-to)552-61
Number of pages10
ISSN1061-4036
DOIs
Publication statusPublished - May 2012
Externally publishedYes

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