Procopio Francesca, Liao Wangjingyi, Rimfeld Kaili, Malanchini Margherita, von Stumm Sophie, Allegrini Andrea G, Plomin Robert
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK.
Mol Psychiatry. 2025 Feb;30(2):414-422. doi: 10.1038/s41380-024-02671-w. Epub 2024 Jul 31.
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.
特定认知能力(SCA)在遗传上的相关性约为0.50,它支撑着一般认知能力(g),但这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特定的,因为它们都充满了g。在此,我们使用双胞胎和DNA研究了独立于g的数学、阅读和语言能力(SCA.g)的遗传度,以及与未校正g的SCA相比,多个全基因组多基因评分(multi-PGS)联合预测这些SCA.g的程度。我们在双胞胎早期发展研究(TEDS)中,根据对5000对12岁双胞胎进行的14项认知测试组合创建了SCA和SCA.g综合指标。单变量双胞胎分析得出,SCA.g的平均遗传度估计值为40%,而未校正的SCA为53%。使用全基因组SNP基因型,基于SNP的SCA.g平均遗传度为26%,SCA为35%。然后,我们使用弹性网惩罚回归模型,从至少50个PGS创建multi-PGS,以预测每个SCA和SCA.g。Multi-PGS平均预测了SCA.g变异的4.4%,而未校正g的SCA为11.1%。SCA.g的双胞胎、SNP和PGS遗传度估计提供了进一步的证据,表明SCA的遗传度不仅仅是g的反映。尽管从SCA到SCA.g,PGS遗传度的遗传度相对降低幅度大于双胞胎或SNP遗传度,但这种下降可能是由于SCA的PGS数量不足。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,这些研究可用于预测独立于g的SCA优势和劣势的PGS概况。