A genome-wide association study identifies genetic loci associated with specific lobar brain volumes

Sven J. van der Lee, Maria J. Knol, Ganesh Chauhan, Claudia L. Satizabal, Albert Vernon Smith, Edith Hofer, Joshua C. Bis, Derrek P. Hibar, Saima Hilal, Erik B. van den Akker, Konstantinos Arfanakis, Manon Bernard, Lisa R. Yanek, Najaf Amin, Fabrice Crivello, Josh W. Cheung, Tamara B. Harris, Yasaman Saba, Oscar L. Lopez, Shuo LiJeroen van der Grond, Lei Yu, Tomas Paus, Gennady V. Roshchupkin, Philippe Amouyel, Neda Jahanshad, Kent D. Taylor, Qiong Yang, Rasika A. Mathias, Stefan Boehringer, Bernard Mazoyer, Ken Rice, Ching Yu Cheng, Pauline Maillard, Diana van Heemst, Tien Yin Wong, Wiro J. Niessen, Alexa S. Beiser, Marian Beekman, Wanting Zhao, Paul A. Nyquist, Christopher Chen, Lenore J. Launer, Bruce M. Psaty, M. Kamran Ikram, Meike W. Vernooij, Helena Schmidt, Zdenka Pausova, Diane M. Becker, Philip L. De Jager, Paul M. Thompson, Cornelia M. van Duijn, David A. Bennett, P. Eline Slagboom, Reinhold Schmidt, W. T. Longstreth, M. Arfan Ikram, Sudha Seshadri, Stéphanie Debette, Vilmundur Gudnason, Hieab H.H. Adams, Charles DeCarli

Research output: Contribution to journalArticle

Abstract

Brain lobar volumes are heritable but genetic studies are limited. We performed genome-wide association studies of frontal, occipital, parietal and temporal lobe volumes in 16,016 individuals, and replicated our findings in 8,789 individuals. We identified six genetic loci associated with specific lobar volumes independent of intracranial volume. Two loci, associated with occipital (6q22.32) and temporal lobe volume (12q14.3), were previously reported to associate with intracranial and hippocampal volume, respectively. We identified four loci previously unknown to affect brain volumes: 3q24 for parietal lobe volume, and 1q22, 4p16.3 and 14q23.1 for occipital lobe volume. The associated variants were located in regions enriched for histone modifications (DAAM1 and THBS3), or close to genes causing Mendelian brain-related diseases (ZIC4 and FGFRL1). No genetic overlap between lobar volumes and neurological or psychiatric diseases was observed. Our findings reveal part of the complex genetics underlying brain development and suggest a role for regulatory regions in determining brain volumes.

Original languageEnglish (US)
Article number285
JournalCommunications Biology
Volume2
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Genetic Loci
Genome-Wide Association Study
Occipital Lobe
Brain
Genes
brain
Parietal Lobe
loci
Temporal Lobe
Histone Code
Nucleic Acid Regulatory Sequences
Brain Diseases
Frontal Lobe
Psychiatry
Density (specific gravity)
Histones
genome-wide association study
histones

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

Cite this

van der Lee, S. J., Knol, M. J., Chauhan, G., Satizabal, C. L., Smith, A. V., Hofer, E., ... DeCarli, C. (2019). A genome-wide association study identifies genetic loci associated with specific lobar brain volumes. Communications Biology, 2(1), [285]. https://doi.org/10.1038/s42003-019-0537-9

A genome-wide association study identifies genetic loci associated with specific lobar brain volumes. / van der Lee, Sven J.; Knol, Maria J.; Chauhan, Ganesh; Satizabal, Claudia L.; Smith, Albert Vernon; Hofer, Edith; Bis, Joshua C.; Hibar, Derrek P.; Hilal, Saima; van den Akker, Erik B.; Arfanakis, Konstantinos; Bernard, Manon; Yanek, Lisa R.; Amin, Najaf; Crivello, Fabrice; Cheung, Josh W.; Harris, Tamara B.; Saba, Yasaman; Lopez, Oscar L.; Li, Shuo; van der Grond, Jeroen; Yu, Lei; Paus, Tomas; Roshchupkin, Gennady V.; Amouyel, Philippe; Jahanshad, Neda; Taylor, Kent D.; Yang, Qiong; Mathias, Rasika A.; Boehringer, Stefan; Mazoyer, Bernard; Rice, Ken; Cheng, Ching Yu; Maillard, Pauline; van Heemst, Diana; Wong, Tien Yin; Niessen, Wiro J.; Beiser, Alexa S.; Beekman, Marian; Zhao, Wanting; Nyquist, Paul A.; Chen, Christopher; Launer, Lenore J.; Psaty, Bruce M.; Ikram, M. Kamran; Vernooij, Meike W.; Schmidt, Helena; Pausova, Zdenka; Becker, Diane M.; De Jager, Philip L.; Thompson, Paul M.; van Duijn, Cornelia M.; Bennett, David A.; Slagboom, P. Eline; Schmidt, Reinhold; Longstreth, W. T.; Ikram, M. Arfan; Seshadri, Sudha; Debette, Stéphanie; Gudnason, Vilmundur; Adams, Hieab H.H.; DeCarli, Charles.

In: Communications Biology, Vol. 2, No. 1, 285, 01.12.2019.

Research output: Contribution to journalArticle

van der Lee, SJ, Knol, MJ, Chauhan, G, Satizabal, CL, Smith, AV, Hofer, E, Bis, JC, Hibar, DP, Hilal, S, van den Akker, EB, Arfanakis, K, Bernard, M, Yanek, LR, Amin, N, Crivello, F, Cheung, JW, Harris, TB, Saba, Y, Lopez, OL, Li, S, van der Grond, J, Yu, L, Paus, T, Roshchupkin, GV, Amouyel, P, Jahanshad, N, Taylor, KD, Yang, Q, Mathias, RA, Boehringer, S, Mazoyer, B, Rice, K, Cheng, CY, Maillard, P, van Heemst, D, Wong, TY, Niessen, WJ, Beiser, AS, Beekman, M, Zhao, W, Nyquist, PA, Chen, C, Launer, LJ, Psaty, BM, Ikram, MK, Vernooij, MW, Schmidt, H, Pausova, Z, Becker, DM, De Jager, PL, Thompson, PM, van Duijn, CM, Bennett, DA, Slagboom, PE, Schmidt, R, Longstreth, WT, Ikram, MA, Seshadri, S, Debette, S, Gudnason, V, Adams, HHH & DeCarli, C 2019, 'A genome-wide association study identifies genetic loci associated with specific lobar brain volumes', Communications Biology, vol. 2, no. 1, 285. https://doi.org/10.1038/s42003-019-0537-9
van der Lee, Sven J. ; Knol, Maria J. ; Chauhan, Ganesh ; Satizabal, Claudia L. ; Smith, Albert Vernon ; Hofer, Edith ; Bis, Joshua C. ; Hibar, Derrek P. ; Hilal, Saima ; van den Akker, Erik B. ; Arfanakis, Konstantinos ; Bernard, Manon ; Yanek, Lisa R. ; Amin, Najaf ; Crivello, Fabrice ; Cheung, Josh W. ; Harris, Tamara B. ; Saba, Yasaman ; Lopez, Oscar L. ; Li, Shuo ; van der Grond, Jeroen ; Yu, Lei ; Paus, Tomas ; Roshchupkin, Gennady V. ; Amouyel, Philippe ; Jahanshad, Neda ; Taylor, Kent D. ; Yang, Qiong ; Mathias, Rasika A. ; Boehringer, Stefan ; Mazoyer, Bernard ; Rice, Ken ; Cheng, Ching Yu ; Maillard, Pauline ; van Heemst, Diana ; Wong, Tien Yin ; Niessen, Wiro J. ; Beiser, Alexa S. ; Beekman, Marian ; Zhao, Wanting ; Nyquist, Paul A. ; Chen, Christopher ; Launer, Lenore J. ; Psaty, Bruce M. ; Ikram, M. Kamran ; Vernooij, Meike W. ; Schmidt, Helena ; Pausova, Zdenka ; Becker, Diane M. ; De Jager, Philip L. ; Thompson, Paul M. ; van Duijn, Cornelia M. ; Bennett, David A. ; Slagboom, P. Eline ; Schmidt, Reinhold ; Longstreth, W. T. ; Ikram, M. Arfan ; Seshadri, Sudha ; Debette, Stéphanie ; Gudnason, Vilmundur ; Adams, Hieab H.H. ; DeCarli, Charles. / A genome-wide association study identifies genetic loci associated with specific lobar brain volumes. In: Communications Biology. 2019 ; Vol. 2, No. 1.
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abstract = "Brain lobar volumes are heritable but genetic studies are limited. We performed genome-wide association studies of frontal, occipital, parietal and temporal lobe volumes in 16,016 individuals, and replicated our findings in 8,789 individuals. We identified six genetic loci associated with specific lobar volumes independent of intracranial volume. Two loci, associated with occipital (6q22.32) and temporal lobe volume (12q14.3), were previously reported to associate with intracranial and hippocampal volume, respectively. We identified four loci previously unknown to affect brain volumes: 3q24 for parietal lobe volume, and 1q22, 4p16.3 and 14q23.1 for occipital lobe volume. The associated variants were located in regions enriched for histone modifications (DAAM1 and THBS3), or close to genes causing Mendelian brain-related diseases (ZIC4 and FGFRL1). No genetic overlap between lobar volumes and neurological or psychiatric diseases was observed. Our findings reveal part of the complex genetics underlying brain development and suggest a role for regulatory regions in determining brain volumes.",
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AU - Knol, Maria J.

AU - Chauhan, Ganesh

AU - Satizabal, Claudia L.

AU - Smith, Albert Vernon

AU - Hofer, Edith

AU - Bis, Joshua C.

AU - Hibar, Derrek P.

AU - Hilal, Saima

AU - van den Akker, Erik B.

AU - Arfanakis, Konstantinos

AU - Bernard, Manon

AU - Yanek, Lisa R.

AU - Amin, Najaf

AU - Crivello, Fabrice

AU - Cheung, Josh W.

AU - Harris, Tamara B.

AU - Saba, Yasaman

AU - Lopez, Oscar L.

AU - Li, Shuo

AU - van der Grond, Jeroen

AU - Yu, Lei

AU - Paus, Tomas

AU - Roshchupkin, Gennady V.

AU - Amouyel, Philippe

AU - Jahanshad, Neda

AU - Taylor, Kent D.

AU - Yang, Qiong

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AU - Boehringer, Stefan

AU - Mazoyer, Bernard

AU - Rice, Ken

AU - Cheng, Ching Yu

AU - Maillard, Pauline

AU - van Heemst, Diana

AU - Wong, Tien Yin

AU - Niessen, Wiro J.

AU - Beiser, Alexa S.

AU - Beekman, Marian

AU - Zhao, Wanting

AU - Nyquist, Paul A.

AU - Chen, Christopher

AU - Launer, Lenore J.

AU - Psaty, Bruce M.

AU - Ikram, M. Kamran

AU - Vernooij, Meike W.

AU - Schmidt, Helena

AU - Pausova, Zdenka

AU - Becker, Diane M.

AU - De Jager, Philip L.

AU - Thompson, Paul M.

AU - van Duijn, Cornelia M.

AU - Bennett, David A.

AU - Slagboom, P. Eline

AU - Schmidt, Reinhold

AU - Longstreth, W. T.

AU - Ikram, M. Arfan

AU - Seshadri, Sudha

AU - Debette, Stéphanie

AU - Gudnason, Vilmundur

AU - Adams, Hieab H.H.

AU - DeCarli, Charles

PY - 2019/12/1

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N2 - Brain lobar volumes are heritable but genetic studies are limited. We performed genome-wide association studies of frontal, occipital, parietal and temporal lobe volumes in 16,016 individuals, and replicated our findings in 8,789 individuals. We identified six genetic loci associated with specific lobar volumes independent of intracranial volume. Two loci, associated with occipital (6q22.32) and temporal lobe volume (12q14.3), were previously reported to associate with intracranial and hippocampal volume, respectively. We identified four loci previously unknown to affect brain volumes: 3q24 for parietal lobe volume, and 1q22, 4p16.3 and 14q23.1 for occipital lobe volume. The associated variants were located in regions enriched for histone modifications (DAAM1 and THBS3), or close to genes causing Mendelian brain-related diseases (ZIC4 and FGFRL1). No genetic overlap between lobar volumes and neurological or psychiatric diseases was observed. Our findings reveal part of the complex genetics underlying brain development and suggest a role for regulatory regions in determining brain volumes.

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