Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia.
Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia.
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DOI：
10.1038/s41380-020-00898-x
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发表时间：
2021-07
影响因子：
11
通讯作者：
Schulte-Körne G
中科院分区：
文献类型：
--
作者：
Gialluisi A;Andlauer TFM;Mirza-Schreiber N;Moll K;Becker J;Hoffmann P;Ludwig KU;Czamara D;Pourcain BS;Honbolygó F;Tóth D;Csépe V;Huguet G;Chaix Y;Iannuzzi S;Demonet JF;Morris AP;Hulslander J;Willcutt EG;DeFries JC;Olson RK;Smith SD;Pennington BF;Vaessen A;Maurer U;Lyytinen H;Peyrard-Janvid M;Leppänen PHT;Brandeis D;Bonte M;Stein JF;Talcott JB;Fauchereau F;Wilcke A;Kirsten H;Müller B;Francks C;Bourgeron T;Monaco AP;Ramus F;Landerl K;Kere J;Scerri TS;Paracchini S;Fisher SE;Schumacher J;Nöthen MM;Müller-Myhsok B;Schulte-Körne G
发展性阅读障碍（DD）是一种影响阅读能力的学习障碍，遗传率为40-60%。这种遗传性的显著部分仍未得到解释，需要进行大量的遗传研究来确定新的易感基因，并阐明阅读障碍的遗传基础。我们对2274例阅读障碍患者和6272名对照者进行了全基因组关联研究（GWAS），在单变异、基因和通路水平上检测相关性，并使用单核苷酸多态性（SNP）数据估计遗传力。我们还基于不同神经精神疾病和皮质脑测量、受教育程度和流体智力的大规模GWAS数据计算了多基因评分（pgs），并在我们的样本中测试了它们与阅读障碍状态的关联。我们观察到，在基因水平上，LOC388780 （20p13；未表征基因）和VEPH1 (3q25)（一个与大脑发育有关的基因）的关联富集具有统计学意义（p < 2.8 × 10−6）。我们估计，DD的snp遗传率为20-25%，并观察到阅读障碍风险与注意缺陷多动障碍（训练GWAS中pT = 0.05: OR = 1.23[1.16； 1.30]每标准差增加，p = 8 × 10 - 13）、双相情感障碍（1.53[1.44;1.63],p = 1 × 10 - 43）、精神分裂症（1.36[1.28;1.45],p = 4 × 10 - 22）、精神交叉障碍易感性（1.23[1.16;1.30]）和pgp显著相关。P = 3 × 10−12)、颞横回皮质厚度（0.90[0.86;0.96];P = 5 × 10−4）、受教育程度（0.86[0.82;0.91];P = 2 × 10−7）和智力（0.72[0.68;0.76];P = 9 × 10−29）。这项研究表明，常见的遗传变异对阅读障碍风险的重要贡献，以及与双相情感障碍、精神分裂症和交叉障碍易感性等精神疾病的新基因组重叠。此外，它揭示了共享的遗传基础的存在与神经相关先前涉及阅读障碍的神经影像学证据。
Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40–60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10−6) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20–25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 × 10−13), bipolar disorder (1.53[1.44; 1.63]; p = 1 × 10−43), schizophrenia (1.36[1.28; 1.45]; p = 4 × 10−22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 × 10−12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 × 10−4), educational attainment (0.86[0.82; 0.91]; p = 2 × 10−7), and intelligence (0.72[0.68; 0.76]; p = 9 × 10−29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.
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影响因子：
4.8
作者：
Cederlof, Martin;Maughan, Barbara;Plomin, Robert
通讯作者：
Plomin, Robert
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
30.8
作者：
Finucane HK;Reshef YA;Anttila V;Slowikowski K;Gusev A;Byrnes A;Gazal S;Loh PR;Lareau C;Shoresh N;Genovese G;Saunders A;Macosko E;Pollack S;Brainstorm Consortium;Perry JRB;Buenrostro JD;Bernstein BE;Raychaudhuri S;McCarroll S;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ