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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.

SUBMITTER: van der Lee SJ 

PROVIDER: S-EPMC6677735 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

van der Lee Sven J SJ   Knol Maria J MJ   Chauhan Ganesh G   Satizabal Claudia L CL   Smith Albert Vernon AV   Hofer Edith E   Bis Joshua C JC   Hibar Derrek P DP   Hilal Saima S   van den Akker Erik B EB   Arfanakis Konstantinos K   Bernard Manon M   Yanek Lisa R LR   Amin Najaf N   Crivello Fabrice F   Cheung Josh W JW   Harris Tamara B TB   Saba Yasaman Y   Lopez Oscar L OL   Li Shuo S   van der Grond Jeroen J   Yu Lei L   Paus Tomas T   Roshchupkin Gennady V GV   Amouyel Philippe P   Jahanshad Neda N   Taylor Kent D KD   Yang Qiong Q   Mathias Rasika A RA   Boehringer Stefan S   Mazoyer Bernard B   Rice Ken K   Cheng Ching Yu CY   Maillard Pauline P   van Heemst Diana D   Wong Tien Yin TY   Niessen Wiro J WJ   Beiser Alexa S AS   Beekman Marian M   Zhao Wanting W   Nyquist Paul A PA   Chen Christopher C   Launer Lenore J LJ   Psaty Bruce M BM   Ikram M Kamran MK   Vernooij Meike W MW   Schmidt Helena H   Pausova Zdenka Z   Becker Diane M DM   De Jager Philip L PL   Thompson Paul M PM   van Duijn Cornelia M CM   Bennett David A DA   Slagboom P Eline PE   Schmidt Reinhold R   Longstreth W T WT   Ikram M Arfan MA   Seshadri Sudha S   Debette Stéphanie S   Gudnason Vilmundur V   Adams Hieab H H HHH   DeCarli Charles C  

Communications biology 20190802


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 hippocamp  ...[more]

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