独立于一般认知能力的数学、阅读和语言能力的多基因分数预测

IF 9.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Psychiatry Pub Date : 2024-07-31 DOI:10.1038/s41380-024-02671-w
Francesca Procopio, Wangjingyi Liao, Kaili Rimfeld, Margherita Malanchini, Sophie von Stumm, Andrea G. Allegrini, Robert Plomin
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引用次数: 0

摘要

特定认知能力(SCA)的遗传相关性约为 0.50,它是一般认知能力(g)的基础,但也意味着存在相当大的遗传特异性。如果不控制 g,那么对特定认知能力的基因组预测就不是真正的特异性,因为它们都与 g 有关。在此,我们利用双胞胎和 DNA 研究了数学、阅读和语言能力与 g 无关的遗传率(SCA.与未校正 g 的 SCA 相比,我们利用双胞胎和 DNA 研究了多个全基因组多基因评分(multi-PGS)在多大程度上可以共同预测这些 SCA.g。我们通过对双胞胎早期发育研究(TEDS)中的 5000 对双胞胎在 12 岁时进行的 14 项认知测试创建了 SCA 和 SCA.g 组合。)单变量双胞胎分析得出,SCA.g 的平均遗传率估计为 40%,而未校正 SCA 的平均遗传率估计为 53%。利用全基因组 SNP 基因型,SCA.g 和 SCA 基于 SNP 的平均遗传率分别为 26% 和 35%。然后,我们从至少 50 个 PGS 中创建了多 PGS,使用弹性网惩罚回归模型预测每种 SCA 和 SCA.g。SCA.g的孪生子、SNP和PGS遗传力估计值进一步证明,SCA的遗传力不仅仅是g的反映。虽然从SCA到SCA.g,PGS遗传力的相对降低幅度大于孪生子或SNP遗传力,但这种降低可能是由于SCA的PGS很少。我们希望这些结果能鼓励研究人员对 SCA(尤其是 SCA.g)进行全基因组关联研究,以用于预测与 g 无关的 SCA 优缺点的 PGS 特征。
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Multi-polygenic score prediction of mathematics, reading, and language abilities independent of general cognitive ability

Specific cognitive abilities (SCA) correlate genetically about 0.50, which underpins general cognitive ability (g), but it also means that there is considerable genetic specificity. If g is not controlled, then genomic prediction of specific cognitive abilities is not truly specific because they are all perfused with g. Here, we investigated the heritability of mathematics, reading, and language ability independent of g (SCA.g) using twins and DNA, and the extent to which multiple genome-wide polygenic scores (multi-PGS) can jointly predict these SCA.g as compared to SCA uncorrected for g. We created SCA and SCA.g composites from a battery of 14 cognitive tests administered at age 12 to 5,000 twin pairs in the Twins Early Development Study (TEDS). Univariate twin analyses yielded an average heritability estimate of 40% for SCA.g, compared to 53% for uncorrected SCA. Using genome-wide SNP genotypes, average SNP-based heritabilities were 26% for SCA.g and 35% for SCA. We then created multi-PGS from at least 50 PGS to predict each SCA and SCA.g using elastic net penalised regression models. Multi-PGS predicted 4.4% of the variance of SCA.g on average, compared to 11.1% for SCA uncorrected for g. The twin, SNP and PGS heritability estimates for SCA.g provide further evidence that the heritabilities of SCA are not merely a reflection of g. Although the relative reduction in heritability from SCA to SCA.g was greater for PGS heritability than for twin or SNP heritability, this decrease is likely due to the paucity of PGS for SCA. We hope that these results encourage researchers to conduct genome-wide association studies of SCA, and especially SCA.g, that can be used to predict PGS profiles of SCA strengths and weaknesses independent of g.

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来源期刊
Molecular Psychiatry
Molecular Psychiatry 医学-精神病学
CiteScore
20.50
自引率
4.50%
发文量
459
审稿时长
4-8 weeks
期刊介绍: Molecular Psychiatry focuses on publishing research that aims to uncover the biological mechanisms behind psychiatric disorders and their treatment. The journal emphasizes studies that bridge pre-clinical and clinical research, covering cellular, molecular, integrative, clinical, imaging, and psychopharmacology levels.
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