Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence.,Cerebral Cortex

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Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence.
Cerebral Cortex ( IF 2.9 ) Pub Date : 2020-04-14 , DOI: 10.1093/cercor/bhz270
Tristram A Lett _{1,

2} , Bob O Vogel ₁ , Stephan Ripke _{1,

3,

4} , Carolin Wackerhagen ₁ , Susanne Erk ₁ , Swapnil Awasthi _{1,

4} , Vassily Trubetskoy _{1,

4} , Eva J Brandl ₁ , Sebastian Mohnke ₁ , Ilya M Veer ₁ , Markus M Nöthen _{5,

6} , Marcella Rietschel ₇ , Franziska Degenhardt _{5,

6} , Nina Romanczuk-Seiferth ₁ , Stephanie H Witt ₇ , Tobias Banaschewski ₈ , Arun L W Bokde ₉ , Christian Büchel ₁₀ , Erin B Quinlan ₁₁ , Sylvane Desrivières ₁₁ , Herta Flor _{12,

13} , Vincent Frouin ₁₄ , Hugh Garavan ₁₅ , Penny Gowland ₁₆ , Bernd Ittermann ₁₇ , Jean-Luc Martinot ₁₈ , Marie-Laure Paillère Martinot ₁₉ , Frauke Nees _{8,

12} , Dimitri Papadopoulos-Orfanos ₁₄ , Tomáš Paus ₂₀ , Luise Poustka ₂₁ , Juliane H Fröhner ₂₂ , Michael N Smolka ₂₂ , Robert Whelan ₂₃ , Gunter Schumann ₁₁ , Heike Tost ₇ , Andreas Meyer-Lindenberg ₇ , Andreas Heinz ₁ , Henrik Walter ₁ ,

Affiliation

Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, 10117 Berlin, Germany.
Department of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, Campus Mitte, 10117 Berlin, Germany.
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany.
Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany.
Central Institute of Mental Health, University of Heidelberg, 68159 Mannheim, Germany.
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, 68159 Mannheim, Germany.
Discipline of Psychiatry, School of Medicine and Trinity College, Institute of Neuroscience, College Green, Dublin 2, Ireland.
University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany.
Centre for Population Neuroscience and Stratified Medicine (PONS) and MRC-SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College De Crespigny Park, London, WC2R 2LS, UK.
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany.
Department of Psychology, School of Social Sciences, University of Mannheim, 68131 Mannheim, Germany.
NeuroSpin, CEA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France.
Departments of Psychiatry and Psychology, University of Vermont, 05405 Burlington, VT, USA.
Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
Physikalisch-Technische Bundesanstalt (PTB), Berlin, Germany.
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry," University Paris Sud, University Paris Descartes - Sorbonne Paris Cité; and Maison de Solenn, Paris, France.
Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud, University Paris Descartes; Sorbonne Université; and AP-HP, Paris, France.
Holland Bloorview Kids Rehabilitation Hospital and Departments of Psychology and Psychiatry, Bloorview Research Institute, University of Toronto, Toronto, Ontario, M6A 2E1, Canada.
Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, 37075, Göttingen, Germany.
Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
School of Psychology and Global Brain Health Institute, Trinity College Dublin, College Green, Dublin 2, Ireland.

Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived polygenic scores for intelligence (PSi) and g-factor. Using the effect sizes from one of the largest GWAS meta-analysis on general intelligence to date, PSi were calculated among 10 P value thresholds. PSi were assessed for the association with g-factor performance, cortical thickness (CT), and surface area (SA) in two large imaging-genetics samples (IMAGEN N = 1651; IntegraMooDS N = 742). PSi explained up to 5.1% of the variance of g-factor in IMAGEN (F1,1640 = 12.2-94.3; P < 0.005), and up to 3.0% in IntegraMooDS (F1,725 = 10.0-21.0; P < 0.005). The association between polygenic scores and g-factor was partially mediated by SA and CT in prefrontal, anterior cingulate, insula, and medial temporal cortices in both samples (PFWER-corrected < 0.005). The variance explained by mediation was up to 0.75% in IMAGEN and 0.77% in IntegraMooDS. Our results provide evidence that cumulative genetic load influences g-factor via cortical structure. The consistency of our results across samples suggests that cortex morphology could be a novel potential biomarker for neurocognitive dysfunction that is among the most intractable psychiatric symptoms.

中文翻译：

皮质表面调节智力多基因评分和一般智力之间的关系。

最近的大规模全基因组关联研究（GWAS）已经确定了数百个与一般智力相关的遗传位点。这些基因座对大脑结构的累积影响尚不清楚。我们检查了皮质形态是否介导 GWAS 衍生的多基因智力评分 (PSi) 和 g 因子之间的关系。使用迄今为止最大的一般智力 GWAS 荟萃分析之一的效应大小，在 10 个 P 值阈值中计算 PSi。在两个大型成像遗传学样本（IMAGEN N = 1651；IntegraMooDS N = 742）中评估了 PSi 与 g 因子性能、皮质厚度 (CT) 和表面积 (SA) 的关联。PSi 在 IMAGEN 中解释了高达 5.1% 的 g 因子方差（F1,1640 = 12.2-94.3；P < 0.005），在 IntegraMooDS 中解释了高达 3.0% 的 g 因子方差（F1,725 = 10.0-21.0；P < 0.005）。多基因评分和 g 因子之间的关联部分由两个样本中前额叶、前扣带回、岛叶和内侧颞叶皮质的 SA 和 CT 介导（PFWER 校正 < 0.005）。由中介解释的方差在 IMAGEN 中高达 0.75%，在 IntegraMooDS 中高达 0.77%。我们的结果提供了累积遗传负荷通过皮质结构影响 g 因子的证据。我们的跨样本结果的一致性表明，皮层形态可能是神经认知功能障碍的一种新的潜在生物标志物，神经认知功能障碍是最棘手的精神症状之一。

更新日期：2020-04-23

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