Large-scale genomics unveil polygenic architecture of human cortical surface area

Chi Hua Chen, Qian Peng, Andrew J. Schork, Min Tzu Lo, Chun Chieh Fan, Yunpeng Wang, Rahul S. Desikan, Francesco Bettella, Donald J. Hagler, Lars T. Westlye, William S. Kremen, Terry L. Jernigan, Stephanie Le Hellard, Vidar M. Steen, Thomas Espeseth, Matt Huentelman, Asta K. Håberg, Ingrid Agartz, Srdjan Djurovic, Ole A. AndreassenNicholas Schork, Anders M. Dale, Connor McCabe, Linda Chang, Natacha Akshoomoff, Erik Newman, Thomas Ernst, Peter Van Zijl, Joshua Kuperman, Sarah Murray, Cinnamon Bloss, Mark Appelbaum, Anthony Gamst, Wesley Thompson, Hauke Bartsch, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, Davie Holtzman, M. Marcel Mesulman, William Potter, Peter J. Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCarli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, Nigel J. Cairns, Erin Householder, Lisa Taylor-Reinwald, Virginia M Y Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Leon Thal, Richard Frank, Neil Buckholtz, Marilyn Albert, John Hsiao

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 languageEnglish (US)
Article number7549
JournalNature Communications
Volume6
DOIs
StatePublished - Jul 20 2015

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polymorphism
nucleotides
Genomics
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Genes
genome
cortexes
genes
brain
Brain
Genome
Auditory Cortex
Temporal Lobe
Prefrontal Cortex
Neuroimaging
Cerebral Cortex
proportion
Imaging techniques

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Chen, C. H., Peng, Q., Schork, A. J., Lo, M. T., Fan, C. C., Wang, Y., ... Hsiao, J. (2015). Large-scale genomics unveil polygenic architecture of human cortical surface area. Nature Communications, 6, [7549]. https://doi.org/10.1038/ncomms8549

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; 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; 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 journalArticle

Chen, CH, Peng, Q, Schork, AJ, Lo, MT, Fan, CC, Wang, Y, Desikan, RS, Bettella, F, Hagler, DJ, Westlye, LT, Kremen, WS, Jernigan, TL, Le Hellard, S, Steen, VM, Espeseth, T, Huentelman, M, Håberg, AK, Agartz, I, Djurovic, S, Andreassen, OA, Schork, N, Dale, AM, McCabe, C, Chang, L, Akshoomoff, N, Newman, E, Ernst, T, Van Zijl, P, Kuperman, J, Murray, S, Bloss, C, Appelbaum, M, Gamst, A, Thompson, W, Bartsch, H, Weiner, M, Aisen, P, Petersen, R, Jack, CR, Jagust, W, Trojanowki, JQ, Toga, AW, Beckett, L, Green, RC, Saykin, A, Morris, J, Shaw, LM, Khachaturian, Z, Sorensen, G, Carrillo, M, Kuller, L, Raichle, M, Paul, S, Davies, P, Fillit, H, Hefti, F, Holtzman, D, Mesulman, MM, Potter, W, Snyder, PJ, Schwartz, A, Montine, T, Thomas, RG, Donohue, M, Walter, S, Gessert, D, Sather, T, Jiminez, G, Harvey, D, Bernstein, M, Fox, N, Thompson, P, Schuff, N, DeCarli, C, Borowski, B, Gunter, J, Senjem, M, Vemuri, P, Jones, D, Kantarci, K, Ward, C, Koeppe, RA, Foster, N, Reiman, EM, Chen, K, Mathis, C, Landau, S, Cairns, NJ, Householder, E, Taylor-Reinwald, L, Lee, VMY, Korecka, M, Figurski, M, Crawford, K, Neu, S, Foroud, T, Potkin, S, Shen, L, Faber, K, Kim, S, Nho, K, Thal, L, Frank, R, Buckholtz, N, Albert, M & Hsiao, J 2015, 'Large-scale genomics unveil polygenic architecture of human cortical surface area', Nature Communications, vol. 6, 7549. https://doi.org/10.1038/ncomms8549
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 ; 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 ; Potkin, Steven ; Shen, Li ; Faber, Kelley ; Kim, Sungeun ; Nho, Kwangsik ; Thal, Leon ; Frank, Richard ; Buckholtz, Neil ; Albert, Marilyn ; Hsiao, John. / Large-scale genomics unveil polygenic architecture of human cortical surface area. In: Nature Communications. 2015 ; Vol. 6.
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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.",
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AU - Peng, Qian

AU - Schork, Andrew J.

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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.

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AU - Thompson, Paul

AU - Schuff, Norbert

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AU - Borowski, Bret

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AU - Jones, David

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AU - Ward, Chad

AU - Koeppe, Robert A.

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AU - Chen, Kewei

AU - Mathis, Chet

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AU - Cairns, Nigel J.

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AU - Taylor-Reinwald, Lisa

AU - Lee, Virginia M Y

AU - Korecka, Magdalena

AU - Figurski, Michal

AU - Crawford, Karen

AU - Neu, Scott

AU - Foroud, Tatiana

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

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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.

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