A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB

Need, Anna C.; Attix, Deborah K.; McEvoy, Jill M.; Cirulli, Elizabeth T.; Linney, Kristen L.; Hunt, Priscilla; Ge, Dongliang; Heinzen, Erin L.; Maia, Jessica M.; Shianna, Kevin V.; Weale, Michael E.; Cherkas, Lynn; Clement, Gail; Spector, Tim D.; Gibson, Greg; Goldstein, David B.

doi:10.1093/hmg/ddp413

Cited by 130 publications

(100 citation statements)

References 107 publications

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“…For example, Symbol Search, with covariates explaining 41% of the total variation, has an effective power of 80% to detect variants explaining at least 5% of the remaining variation in the trait (Supplementary Table 3). Finding that no single common variant has a large effect on these phenotypes is consistent with a separate study we performed on phenotypes related to very specific aspects of memory 27 and with the emerging body of evidence that many key human phenotypes under long-term selection are not heavily dependent on common variation in individually detectable polymorphisms.…”

Section: Discussionsupporting

confidence: 85%

Common genetic variation and performance on standardized cognitive tests

et al. 2010

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One surprising feature of the recently completed waves of genome-wide association studies is the limited impact of common genetic variation in individually detectable polymorphisms on many human traits. This has been particularly pronounced for studies on psychiatric conditions, which have failed to produce clear, replicable associations for common variants. One popular explanation for these negative findings is that many of these traits may be genetically heterogeneous, leading to the idea that relevant endophenotypes may be more genetically tractable. Aspects of cognition may be the most important endophenotypes for psychiatric conditions such as schizophrenia, leading many researchers to pursue large-scale studies on the genetic contributors of cognitive performance in the normal population as a surrogate for aspects of liability to disease. Here, we perform a genomewide association study with two tests of executive function, Digit Symbol and Stroop Color-Word, in 1086 healthy volunteers and with an expanded cognitive battery in 514 of these volunteers. We show that, consistent with published studies of the psychiatric conditions themselves, no single common variant has a large effect (explaining 44-8% of the population variation) on the performance of healthy individuals on standardized cognitive tests. Given that these are important endophenotypes, our work is consistent with the idea that identifying rare genetic causes of psychiatric conditions may be more important for future research than identifying genetically homogenous endophenotypes.

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Section: Discussionsupporting

confidence: 85%

Common genetic variation and performance on standardized cognitive tests

et al. 2010

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“…Despite the high heritability of intelligence, 12,28,37,38 the progress in the identification of loci consistently associated with variation in its normal range has thus far been limited. 15,17,[38][39][40][41][42] Exceptions are the apolipoprotein E (APOE) gene at older ages 43 and formin binding protein 1-like (FNBP1L), the latter having recently been shown to be associated with both childhood and adulthood intelligence. 15,17 The present approach utilizes the idea that the differentially sized effects of individual mutations located within a gene functionally relevant to the phenotype may range from severe disruptions of protein functioning (resulting in a Mendelian disorder) to smaller effects underlying polygenic variation.…”

Section: Discussionmentioning

confidence: 99%

Intelligence: shared genetic basis between Mendelian disorders and a polygenic trait

et al. 2015

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Multiple inquiries into the genetic etiology of human traits indicated an overlap between genes underlying monogenic disorders (eg, skeletal growth defects) and those affecting continuous variability of related quantitative traits (eg, height). Extending the idea of a shared genetic basis between a Mendelian disorder and a classic polygenic trait, we performed an association study to examine the effect of 43 genes implicated in autosomal recessive cognitive disorders on intelligence in an unselected Dutch population (N = 1316). Using both single-nucleotide polymorphism (SNP)-and gene-based association testing, we detected an association between intelligence and the genes of interest, with genes ELP2, TMEM135, PRMT10, and RGS7 showing the strongest associations. This is a demonstration of the relevance of genes implicated in monogenic disorders of intelligence to normal-range intelligence, and a corroboration of the utility of employing knowledge on monogenic disorders in identifying the genetic variability underlying complex traits.

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“…5d and Supplementary Fig. 11) and two poorly characterized loci associated with neurodevelopmental disorders 34,35 . Having qualitatively validated forebrain HPT, we used EFilter to predict mRNA levels in seven additional cell types (NPC, embryonic stem (ES) cell, mouse embryonic fibroblast, B-cell, myoblast, myotube and 3T3-L1 pre-adipocyte), based on H3K4me3 and H3K36me3 ChIP-seq data from previous studies 31,33,36,37 .…”

Section: Npgmentioning

confidence: 99%