Abstract
Little is known about how genetic variation contributes to neuroanatomical variability, and whether particular genomic regions comprising genes or evolutionarily conserved elements are enriched for effects that influence brain morphology. Here, we examine brain imaging and single-nucleotide polymorphisms (SNPs) data from ∼ 2,700 individuals. We show that a substantial proportion of variation in cortical surface area is explained by additive effects of SNPs dispersed throughout the genome, with a larger heritable effect for visual and auditory sensory and insular cortices (h2 ∼ 0.45). Genome-wide SNPs collectively account for, on average, about half of twin heritability across cortical regions (N = 466 twins). We find enriched genetic effects in or near genes. We also observe that SNPs in evolutionarily more conserved regions contributed significantly to the heritability of cortical surface area, particularly, for medial and temporal cortical regions. SNPs in less conserved regions contributed more to occipital and dorsolateral prefrontal cortices.
| Original language | English |
|---|---|
| Article number | 7549 |
| Journal | Nature communications |
| Volume | 6 |
| DOIs | |
| State | Published - Jul 20 2015 |
Fingerprint
Dive into the research topics of 'Large-scale genomics unveil polygenic architecture of human cortical surface area'. Together they form a unique fingerprint.Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
Large-scale genomics unveil polygenic architecture of human cortical surface area. / Chen, Chi Hua; Peng, Qian; Schork, Andrew J.; Lo, Min Tzu; Fan, Chun Chieh; Wang, Yunpeng; Desikan, Rahul S.; Bettella, Francesco; Hagler, Donald J.; Westlye, Lars T.; Kremen, William S.; Jernigan, Terry L.; Le Hellard, Stephanie; Steen, Vidar M.; Espeseth, Thomas; Huentelman, Matt; Håberg, Asta K.; Agartz, Ingrid; Djurovic, Srdjan; Andreassen, Ole A.; Schork, Nicholas; Dale, Anders M.; McCabe, Connor; Chang, Linda; Akshoomoff, Natacha; Newman, Erik; Ernst, Thomas; Van Zijl, Peter; Kuperman, Joshua; Murray, Sarah; Bloss, Cinnamon; Appelbaum, Mark; Gamst, Anthony; Thompson, Wesley; Bartsch, Hauke; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Khachaturian, Zaven; Sorensen, Greg; Carrillo, Maria; Kuller, Lew; Raichle, Marc; Paul, Steven; Davies, Peter; Fillit, Howard; Hefti, Franz; Holtzman, Davie; Mesulman, M. Marcel; Potter, William; Snyder, Peter J.; Schwartz, Adam; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; DeCarli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor-Reinwald, Lisa; Lee, Virginia M.Y.; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Thal, Leon; Frank, Richard; Buckholtz, Neil; Albert, Marilyn; Hsiao, John.
In: Nature communications, Vol. 6, 7549, 20.07.2015.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Large-scale genomics unveil polygenic architecture of human cortical surface area
AU - Chen, Chi Hua
AU - Peng, Qian
AU - Schork, Andrew J.
AU - Lo, Min Tzu
AU - Fan, Chun Chieh
AU - Wang, Yunpeng
AU - Desikan, Rahul S.
AU - Bettella, Francesco
AU - Hagler, Donald J.
AU - Westlye, Lars T.
AU - Kremen, William S.
AU - Jernigan, Terry L.
AU - Le Hellard, Stephanie
AU - Steen, Vidar M.
AU - Espeseth, Thomas
AU - Huentelman, Matt
AU - Håberg, Asta K.
AU - Agartz, Ingrid
AU - Djurovic, Srdjan
AU - Andreassen, Ole A.
AU - Schork, Nicholas
AU - Dale, Anders M.
AU - McCabe, Connor
AU - Chang, Linda
AU - Akshoomoff, Natacha
AU - Newman, Erik
AU - Ernst, Thomas
AU - Van Zijl, Peter
AU - Kuperman, Joshua
AU - Murray, Sarah
AU - Bloss, Cinnamon
AU - Appelbaum, Mark
AU - Gamst, Anthony
AU - Thompson, Wesley
AU - Bartsch, Hauke
AU - Weiner, Michael
AU - Aisen, Paul
AU - Petersen, Ronald
AU - Jack, Clifford R.
AU - Jagust, William
AU - Trojanowki, John Q.
AU - Toga, Arthur W.
AU - Beckett, Laurel
AU - Green, Robert C.
AU - Saykin, Andrew J.
AU - Morris, John
AU - Shaw, Leslie M.
AU - Khachaturian, Zaven
AU - Sorensen, Greg
AU - Carrillo, Maria
AU - Kuller, Lew
AU - Raichle, Marc
AU - Paul, Steven
AU - Davies, Peter
AU - Fillit, Howard
AU - Hefti, Franz
AU - Holtzman, Davie
AU - Mesulman, M. Marcel
AU - Potter, William
AU - Snyder, Peter J.
AU - Schwartz, Adam
AU - Montine, Tom
AU - Thomas, Ronald G.
AU - Donohue, Michael
AU - Walter, Sarah
AU - Gessert, Devon
AU - Sather, Tamie
AU - Jiminez, Gus
AU - Harvey, Danielle
AU - Bernstein, Matthew
AU - Fox, Nick
AU - Thompson, Paul
AU - Schuff, Norbert
AU - DeCarli, Charles
AU - Borowski, Bret
AU - Gunter, Jeff
AU - Senjem, Matt
AU - Vemuri, Prashanthi
AU - Jones, David
AU - Kantarci, Kejal
AU - Ward, Chad
AU - Koeppe, Robert A.
AU - Foster, Norm
AU - Reiman, Eric M.
AU - Chen, Kewei
AU - Mathis, Chet
AU - Landau, Susan
AU - Cairns, Nigel J.
AU - Householder, Erin
AU - Taylor-Reinwald, Lisa
AU - Lee, Virginia M.Y.
AU - Korecka, Magdalena
AU - Figurski, Michal
AU - Crawford, Karen
AU - Neu, Scott
AU - Foroud, Tatiana M.
AU - Potkin, Steven
AU - Shen, Li
AU - Faber, Kelley
AU - Kim, Sungeun
AU - Nho, Kwangsik
AU - Thal, Leon
AU - Frank, Richard
AU - Buckholtz, Neil
AU - Albert, Marilyn
AU - Hsiao, John
N1 - Funding Information: Funded by the National Institute of Mental Health R01MH100351; National Institute on Aging R01AG22381, AG18386 and AG18384; NARSAD Young Investigator award (C.-H.C). Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, HUNT administration grants, and National Norwegian Advisory Unit, for functional MRI methods. South East Norway Health Authority (#2013-123), Research Council of Norway (#229129, #213837 and #223273), EU (#602450) and KG Jebsen Foundation. Part of data collection and sharing for this project was funded by the Pediatric Imaging, Neurocognition and Genetics Study (PING), National Institutes of Health Grant RC2DA029475. PING is funded by the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health & Human Development. PING data are disseminated by the PING Coordinating Center at the Center for Human Development, University of California, San Diego. Part of data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering and through generous contributions from the following: Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Publisher Copyright: © 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/7/20
Y1 - 2015/7/20
N2 - Little is known about how genetic variation contributes to neuroanatomical variability, and whether particular genomic regions comprising genes or evolutionarily conserved elements are enriched for effects that influence brain morphology. Here, we examine brain imaging and single-nucleotide polymorphisms (SNPs) data from ∼ 2,700 individuals. We show that a substantial proportion of variation in cortical surface area is explained by additive effects of SNPs dispersed throughout the genome, with a larger heritable effect for visual and auditory sensory and insular cortices (h2 ∼ 0.45). Genome-wide SNPs collectively account for, on average, about half of twin heritability across cortical regions (N = 466 twins). We find enriched genetic effects in or near genes. We also observe that SNPs in evolutionarily more conserved regions contributed significantly to the heritability of cortical surface area, particularly, for medial and temporal cortical regions. SNPs in less conserved regions contributed more to occipital and dorsolateral prefrontal cortices.
AB - Little is known about how genetic variation contributes to neuroanatomical variability, and whether particular genomic regions comprising genes or evolutionarily conserved elements are enriched for effects that influence brain morphology. Here, we examine brain imaging and single-nucleotide polymorphisms (SNPs) data from ∼ 2,700 individuals. We show that a substantial proportion of variation in cortical surface area is explained by additive effects of SNPs dispersed throughout the genome, with a larger heritable effect for visual and auditory sensory and insular cortices (h2 ∼ 0.45). Genome-wide SNPs collectively account for, on average, about half of twin heritability across cortical regions (N = 466 twins). We find enriched genetic effects in or near genes. We also observe that SNPs in evolutionarily more conserved regions contributed significantly to the heritability of cortical surface area, particularly, for medial and temporal cortical regions. SNPs in less conserved regions contributed more to occipital and dorsolateral prefrontal cortices.
UR - http://www.scopus.com/inward/record.url?scp=84937413458&partnerID=8YFLogxK
U2 - 10.1038/ncomms8549
DO - 10.1038/ncomms8549
M3 - Article
C2 - 26189703
AN - SCOPUS:84937413458
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 7549
ER -