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<p>Reading disorder (RD), characterized by difficulties in reading, is the most common learning disability and frequently co-occurs with attention-deficit/hyperactivity disorder (ADHD), suggesting shared genetic underpinnings. To investigate their genetic overlap, we leveraged summary statistics from large-scale genome-wide association studies (GWASs) of reading assessment scores and ADHD diagnosis using genomic structural equation modeling. We modeled a common genetic factor capturing shared genetic influences between reading-related traits and ADHD. GWAS of this common factor revealed a pleiotropic locus on chromosome 12 (rs7969091, <InlineEquation ID="IEq1"><EquationSource Format="TEX">\(\beta\)</EquationSource><EquationSource Format="MATHML"><math><mi>β</mi></math></EquationSource></InlineEquation> = −0.035, <InlineEquation ID="IEq2"><EquationSource Format="TEX">\(p\)</EquationSource><EquationSource Format="MATHML"><math><mi>p</mi></math></EquationSource></InlineEquation> = 3.86 × 10<sup>−8</sup>). Transcriptome-wide structural equation modeling analysis identified associations with tissue-specific expression of <i>RHEBL1</i> and <i>LMBR1L</i> within the same locus as GWAS hit. Genetic correlation analyses showed significant correlations of the common factor with six psychiatric disorders (<i>r</i><sub>g</sub> = −0.47 to 0.24) and six behavioral traits (<i>r</i><sub>g</sub> = 0.31 to 0.74). Our findings provide novel insights into the shared genetic underpinnings of RD and ADHD.</p>

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Shared genetic architecture of reading and attention disorders using genomic structural equation modeling

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月2日

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  • Shiying Wang,
  • Joan Bosson-Heenan,
  • Andrew Grotzinger,
  • Jan C. Frijters,
  • Jeffrey R. Gruen

摘要

Reading disorder (RD), characterized by difficulties in reading, is the most common learning disability and frequently co-occurs with attention-deficit/hyperactivity disorder (ADHD), suggesting shared genetic underpinnings. To investigate their genetic overlap, we leveraged summary statistics from large-scale genome-wide association studies (GWASs) of reading assessment scores and ADHD diagnosis using genomic structural equation modeling. We modeled a common genetic factor capturing shared genetic influences between reading-related traits and ADHD. GWAS of this common factor revealed a pleiotropic locus on chromosome 12 (rs7969091, \(\beta\)β = −0.035, \(p\)p = 3.86 × 10−8). Transcriptome-wide structural equation modeling analysis identified associations with tissue-specific expression of RHEBL1 and LMBR1L within the same locus as GWAS hit. Genetic correlation analyses showed significant correlations of the common factor with six psychiatric disorders (rg = −0.47 to 0.24) and six behavioral traits (rg = 0.31 to 0.74). Our findings provide novel insights into the shared genetic underpinnings of RD and ADHD.