Genetic control of variability in subcortical and intracranial volumes.,Molecular Psychiatry

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Genetic control of variability in subcortical and intracranial volumes.
Molecular Psychiatry ( IF 9.6 ) Pub Date : 2020-02-11 , DOI: 10.1038/s41380-020-0664-1
Aldo Córdova-Palomera ₁ , Dennis van der Meer _{1,

2} , Tobias Kaufmann ₁ , Francesco Bettella ₁ , Yunpeng Wang _{1,

3} , Dag Alnæs ₁ , Nhat Trung Doan ₁ , Ingrid Agartz _{4,

5,

6} , Alessandro Bertolino _{7,

8} , Jan K Buitelaar _{9,

10} , David Coynel _{11,

12} , Srdjan Djurovic _{13,

14} , Erlend S Dørum _{1,

15,

16} , Thomas Espeseth ₁₅ , Leonardo Fazio ₈ , Barbara Franke ₁₇ , Oleksandr Frei ₁ , Asta Håberg _{18,

19} , Stephanie Le Hellard ₁₃ , Erik G Jönsson _{1,

5} , Knut K Kolskår _{1,

15,

16} , Martina J Lund ₁ , Torgeir Moberget _{1,

15} , Jan E Nordvik ₂₀ , Lars Nyberg ₂₁ , Andreas Papassotiropoulos _{11,

22,

23} , Giulio Pergola ₈ , Dominique de Quervain _{11,

12} , Antonio Rampino ₈ , Genevieve Richard _{1,

15,

16} , Jaroslav Rokicki _{1,

15} , Anne-Marthe Sanders _{1,

15,

16} , Emanuel Schwarz ₂₄ , Olav B Smeland ₁ , Vidar M Steen _{13,

25} , Jostein Starrfelt ₂₆ , Ida E Sønderby _{1,

14} , Kristine M Ulrichsen _{1,

15,

16} , Ole A Andreassen ₁ , Lars T Westlye _{1,

15}

Affiliation

NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo, Oslo, Norway.
Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway.
Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
NORMENT, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Institute of Psychiatry, Bari University Hospital, Bari, Italy.
Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland.
Division of Cognitive Neuroscience, University of Basel, Basel, Switzerland.
NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Department of Psychology, University of Oslo, Oslo, Norway.
Sunnaas Rehabilitation Hospital HT, Nesodden, Norway.
Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim, Norway.
CatoSenteret Rehabilitation Center, Son, Norway.
Department of Radiation Sciences, Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden.
Division of Molecular Neuroscience, University of Basel, Basel, Switzerland.
Life Sciences Training Facility, Department Biozentrum, University of Basel, Basel, Switzerland.
Central Institute of Mental Health, Heidelberg University, Mannheim, Germany.
Dr. E. Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, Oslo, Norway.

Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8-89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.

中文翻译：

皮质下和颅内体积变异性的遗传控制。

对外部需求的敏感性对于适应动态环境至关重要，但其代价是在面对恶劣的环境条件时出现不利结果的风险增加。在这里，我们应用一种新的方法对十个关键大脑特征（伏隔核、杏仁核、尾状核、海马体、苍白球、壳核、丘脑、颅内体积、皮质表面积和皮质厚度）的均值和方差进行全基因组关联分析，整合来自大型寿命样本（n = 25,575 人；8-89 岁，平均年龄 51.9 岁）的遗传和神经解剖学数据。我们确定了与丘脑体积和皮质厚度的表型变异相关的遗传位点。方差控制基因座涉及在大脑和心理健康中具有记录作用的基因，并且与平均解剖体积无关。

更新日期：2020-02-11

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