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 Li; Jeroen 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

doi:https://doi.org/10.1038/s42003-019-0537-9

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

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19 Citations (Scopus)

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 language	English
Article number	285
Journal	Communications Biology
Volume	2
Issue number	1
DOIs	https://doi.org/10.1038/s42003-019-0537-9
Publication status	Published - 1 Dec 2019
Externally published	Yes

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van der Lee, S. J., Knol, M. J., Chauhan, G., Satizabal, C. L., Smith, A. V., Hofer, E., Bis, J. C., Hibar, D. P., Hilal, S., van den Akker, E. B., Arfanakis, K., Bernard, M., Yanek, L. R., Amin, N., Crivello, F., Cheung, J. W., Harris, T. B., Saba, Y., Lopez, O. L., ... 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

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title = "A genome-wide association study identifies genetic loci associated with specific lobar brain volumes",

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.",

author = "{van der Lee}, {Sven J.} and Knol, {Maria J.} and Ganesh Chauhan and Satizabal, {Claudia L.} and Smith, {Albert Vernon} and Edith Hofer and Bis, {Joshua C.} and Hibar, {Derrek P.} and Saima Hilal and {van den Akker}, {Erik B.} and Konstantinos Arfanakis and Manon Bernard and Yanek, {Lisa R.} and Najaf Amin and Fabrice Crivello and Cheung, {Josh W.} and Harris, {Tamara B.} and Yasaman Saba and Lopez, {Oscar L.} and Shuo Li and {van der Grond}, Jeroen and Lei Yu and Tomas Paus and Roshchupkin, {Gennady V.} and Philippe Amouyel and Neda Jahanshad and Taylor, {Kent D.} and Qiong Yang and Mathias, {Rasika A.} and Stefan Boehringer and Bernard Mazoyer and Ken Rice and Cheng, {Ching Yu} and Pauline Maillard and {van Heemst}, Diana and Wong, {Tien Yin} and Niessen, {Wiro J.} and Beiser, {Alexa S.} and Marian Beekman and Wanting Zhao and Nyquist, {Paul A.} and Christopher Chen and Launer, {Lenore J.} and Psaty, {Bruce M.} and Ikram, {M. Kamran} and Vernooij, {Meike W.} and Helena Schmidt and Zdenka Pausova and Becker, {Diane M.} and {de Jager}, {Philip L.} and Thompson, {Paul M.} and {van Duijn}, {Cornelia M.} and Bennett, {David A.} and Slagboom, {P. Eline} and Reinhold Schmidt and Longstreth, {W. T.} and Ikram, {M. Arfan} and Sudha Seshadri and St{\'e}phanie Debette and Vilmundur Gudnason and Adams, {Hieab H. H.} and Charles DeCarli",

year = "2019",

month = dec,

day = "1",

doi = "https://doi.org/10.1038/s42003-019-0537-9",

language = "English",

volume = "2",

journal = "Communications biology",

issn = "2399-3642",

publisher = "Nature Research",

number = "1",

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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

TY - JOUR

T1 - A genome-wide association study identifies genetic loci associated with specific lobar brain volumes

AU - van der Lee, Sven J.

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

AU - Mathias, Rasika A.

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

Y1 - 2019/12/1

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.

AB - 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85071153870&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/31396565

U2 - https://doi.org/10.1038/s42003-019-0537-9

DO - https://doi.org/10.1038/s42003-019-0537-9

M3 - Article

C2 - 31396565

SN - 2399-3642

VL - 2

JO - Communications biology

JF - Communications biology

IS - 1

M1 - 285

ER -

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

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