ORCID Profile
0000-0002-1153-9007
Current Organisation
The University of Edinburgh
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Publisher: Elsevier BV
Date: 11-1994
Publisher: Cambridge University Press (CUP)
Date: 13-03-2018
DOI: 10.1017/THG.2018.11
Abstract: Research on environmental and genetic pathways to complex traits such as educational attainment (EA) is confounded by uncertainty over whether correlations reflect effects of transmitted parental genes, causal family environments, or some, possibly interactive, mixture of both. Thus, an aggregate of thousands of alleles associated with EA (a polygenic risk score PRS) may tap parental behaviors and home environments promoting EA in the offspring. New methods for unpicking and determining these causal pathways are required. Here, we utilize the fact that parents pass, at random, 50% of their genome to a given offspring to create independent scores for the transmitted alleles (conventional EA PRS) and a parental score based on alleles not transmitted to the offspring (EA VP_PRS). The formal effect of non-transmitted alleles on offspring attainment was tested in 2,333 genotyped twins for whom high-quality measures of EA, assessed at age 17 years, were available, and whose parents were also genotyped. Four key findings were observed. First, the EA PRS and EA VP_PRS were empirically independent, validating the virtual-parent design. Second, in this family-based design, children's own EA PRS significantly predicted their EA (β = 0.15), ruling out stratification confounds as a cause of the association of attainment with the EA PRS. Third, parental EA PRS predicted the SES environment parents provided to offspring (β = 0.20), and parental SES and offspring EA were significantly associated (β = 0.33). This would suggest that the EA PRS is at least as strongly linked to social competence as it is to EA, leading to higher attained SES in parents and, therefore, a higher experienced SES for children. In a full structural equation model taking account of family genetic relatedness across multiple siblings the non-transmitted allele effects were estimated at similar values but, in this more complex model, confidence intervals included zero. A test using the forthcoming EA3 PRS may clarify this outcome. The virtual-parent method may be applied to clarify causality in other phenotypes where observational evidence suggests parenting may moderate expression of other outcomes, for instance in psychiatry.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Springer Science and Business Media LLC
Date: 22-11-2007
Abstract: We report the first genome-wide linkage analysis for reading and spelling in a s le of 403 families of twins, aged between 12 and 25 years taken from the normal population and unselected for reading ability. These traits showed heritabilities of 0.52-0.73, and support for linkage exceeded replication levels (lod > 1.44) of seven of the 11 linkages reported in dyslexic s les, namely: 2q22.3, 3p12-q13, 6q11.2, 7q32, 15q21.1, 18p21, and Xq27.3. For five of these (2q22.3, 6q11.2, 7q32, 18p21, and Xq27), this study provides the first independent replication. 1p34-36 and 2p15-16 received some support, with lods of 1.2 and 0.83, respectively, whereas two regions received little support (6p23-21.3 and 11p15.5). This study also identified two novel linkages at 4p15.33-16.1 and 17p13.3, which received suggestive support (max. lod 2.08 and 1.99, respectively).
Publisher: Wiley
Date: 17-01-2006
Publisher: Elsevier BV
Date: 10-2007
Publisher: Wiley
Date: 20-06-2013
DOI: 10.1111/GBB.12053
Publisher: Wiley
Date: 31-05-2018
DOI: 10.1111/ADD.14252
Publisher: Springer Science and Business Media LLC
Date: 15-07-2017
Publisher: Elsevier BV
Date: 04-2001
Publisher: Springer Science and Business Media LLC
Date: 10-11-2013
Publisher: Elsevier BV
Date: 05-2005
Publisher: Springer Science and Business Media LLC
Date: 06-05-2009
DOI: 10.1007/S10519-009-9274-Z
Abstract: Cognitive ability has a substantial genetic component and more than 15 candidate genes have been identified over the past 8 years. One gene that has been associated with general cognitive ability is the cholinergic muscarinic 2 receptor (CHRM2). In an attempt to replicate this finding we typed marker rs8191992 (the originally reported CHRM2 SNP) in two population based cohorts-one Scottish aged over 50 years (N = 2,091) and the other English comprising non-demented elderly participants (N = 758)-and a family-based Australian adolescent s le (N = 1,537). An additional 29 SNPs in CHRM2 were typed in the Australian s le and a further seven in the English cohort. No significant association was found between CHRM2 and erse measures of cognitive ability in any of the s les. In conclusion, this study does not support a role for CHRM2 in cognitive ability.
Publisher: Informa UK Limited
Date: 2004
Publisher: Springer Science and Business Media LLC
Date: 21-05-2008
Abstract: A 5-single nucleotide polymorphism (SNP) set has been associated with general cognitive ability in 5000 7-year-old children from the Twins Early Development Study (TEDS). Four of these SNPs were identified through a 10 K microarray analysis and one was identified through a targeted analysis of brain-expressed genes. The present study tested this association with general cognitive ability in six population s les of varying size and age from Australia, the UK (Scotland and England) and the Netherlands. Results from the largest s le (N=1310) approached significance (P=0.06) in the direction of the original finding, but results from the other s les (N=205-758) were mixed. A meta-analysis of the results--allowing for effect size heterogeneity between s les--yielded a non-significant correlation (r=-0.01, P=0.57), indicating that this SNP set was not associated with general cognitive ability in the populations studied.
Publisher: Elsevier BV
Date: 02-1995
Publisher: Informa UK Limited
Date: 12-2006
Publisher: Frontiers Media SA
Date: 18-03-2019
Publisher: Cambridge University Press (CUP)
Date: 06-2011
Abstract: A set of 10 SNPs associated with reading ability in 7-year-olds was reported based on initial pooled analyses of 100K SNP chip data, with follow-up testing stages using pooling and in idual testing. Here we examine this association in an adolescent population s le of Australian twins and siblings ( N = 1177) aged 12 to 25 years. One (rs1842129) of the 10 SNPs approached significance ( P = .05) but no support was found for the remaining 9 SNPs or the SNP set itself. Results indicate that these SNPs are not associated with reading ability in an Australian population. The results are interpreted as supporting use of much larger SNP sets in common disorders where effects are small.
Publisher: Springer Science and Business Media LLC
Date: 03-1994
DOI: 10.1007/BF02244860
Publisher: Elsevier BV
Date: 11-2008
Publisher: Informa UK Limited
Date: 10-2006
DOI: 10.1207/S15327752JPA8703_10
Abstract: We examined the factor structure of the Schizotypal Personality Questionnaire (SPQ Raine, 1991), using confirmatory factor analysis in 3 experiments, with an aim to better understand the construct of schizotypy. In Experiment 1 we tested the fit of 2-, 3-, and 4-factor models on SPQ data from a normal s le. The paranoid 4-factor model fit the data best but not adequately. Based on the strong basis for the Raine 3-factor model we attempted to improve the fit of the 3-factor model by making 3 modifications to the Raine model. These modifications produced a well-fitting model. In Experiment 2 the good fit of this modified 2-factor model to SPQ scores was replicated in an independent normal s le. In Experiment 3, the modified 3-factor model was successfully extended to include the 3 Chapman schizotypy scales. Together these 3 experiments indicate that the 3-factor model of the SPQ, albeit with some slight modifications, is a good model for schizotypy structure that is not restricted to 1 measure of schizotypal personality traits.
Publisher: Springer Science and Business Media LLC
Date: 07-01-2014
DOI: 10.1038/TP.2013.114
Abstract: Differences in general cognitive ability (intelligence) account for approximately half of the variation in any large battery of cognitive tests and are predictive of important life events including health. Genome-wide analyses of common single-nucleotide polymorphisms indicate that they jointly tag between a quarter and a half of the variance in intelligence. However, no single polymorphism has been reliably associated with variation in intelligence. It remains possible that these many small effects might be aggregated in networks of functionally linked genes. Here, we tested a network of 1461 genes in the postsynaptic density and associated complexes for an enriched association with intelligence. These were ascertained in 3511 in iduals (the Cognitive Ageing Genetics in England and Scotland (CAGES) consortium) phenotyped for general cognitive ability, fluid cognitive ability, crystallised cognitive ability, memory and speed of processing. By analysing the results of a genome wide association study (GWAS) using Gene Set Enrichment Analysis, a significant enrichment was found for fluid cognitive ability for the proteins found in the complexes of N -methyl-D-aspartate receptor complex P =0.002. Replication was sought in two additional cohorts ( N =670 and 2062). A meta-analytic P -value of 0.003 was found when these were combined with the CAGES consortium. The results suggest that genetic variation in the macromolecular machines formed by membrane-associated guanylate kinase (MAGUK) scaffold proteins and their interaction partners contributes to variation in intelligence.
Publisher: Springer Science and Business Media LLC
Date: 15-10-2011
DOI: 10.1007/S10519-010-9402-9
Abstract: The region containing ROBO1 (Chromosome 3p12.3) has been implicated as a susceptibility gene for reading disorder and language deficit by translocation and linkage data. No association studies have yet been reported supporting any candidate gene. Here we report the first association of this gene with language deficits, specifically with phonological buffer deficits (a phenotype implicated in language acquisition, Specific Language Impairment and Speech Sound Disorder) and dyslexia (reading and spelling ability traits) in an unselected s le of adolescent twins and their siblings. Family-based analyses were performed on 144 tag SNPs in ROBO1, typed in 538 families with up to five offspring and tested for association with a developmental marker of language impairment (phonological buffer capacity, assessed using non word repetition). A reading and spelling ability measure--based on validated measures of lexical processing (irregular word) and grapheme-phoneme decoding (pseudo word)--and measures of short-term and working memory were also analysed. Significant association for phonological buffer capacity was observed for 21 of 144 SNPs tested, peaking at 8.70 × 10(-05) and 9.30 × 10(-05) for SNPs rs6803202 and rs4535189 respectively for nonword repetition, values that survive correction for multiple testing. Twenty-two SNPs showed significant associations for verbal storage (forward digit span)--a trait linked to phonological span. By contrast, just 5 SNPs reached nominal significance for working-memory, not surviving correction, and, importantly, only one SNP in the 144 tested reached nominal significance (0.04) for association with reading and spelling ability. These results provide strong support for ROBO1 as a gene involved in a core trait underpinning language acquisition, with a specific function in supporting a short-term buffer for arbitrary phonological strings. These effects of ROBO1 appear to be unrelated to brain mechanisms underpinning reading ability, at least by adolescence. While replication will be critical, the present results strongly support ROBO1 as the first gene discovered to be associated with language deficits affecting normal variation in language ability. Its functional role in neuronal migration underlying bilateral symmetry and lateralization of neuronal function further suggests a role in the evolution of human language ability.
Publisher: Informa UK Limited
Date: 09-2006
Publisher: Elsevier BV
Date: 1995
Publisher: Springer Science and Business Media LLC
Date: 06-1995
DOI: 10.1007/BF02246296
Abstract: To evaluate the consumption of the direct health resources of primary care (PC) in Spain by a cohort of patients with chronic bronchial pathology: chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). Prospective cohort study of patients with CB and COPD monitored in PC in Spain. The first 10 adult patients who attended at random each researcher's clinic and who were diagnosed as suffering an exacerbation of their chronic bronchial pathology were included. Scheduled follow-up visits for a year evaluated the cohort's consumption of health resources. Direct health costs were analysed. 268 doctors, with 2414 patients, took part. 1510 patients completed the 12 months follow-up (62.6%). All the patients received pharmacological treatment for their pulmonary disease. The most common complementary investigations performed were: general blood analysis (1.5 per patient/year), chest x-ray (1.2) and ECG (0.9), followed by spirometry (0.5) and arterial gasometry (0.4). Mean number of exacerbations per year were 1.9 and admissions, 0.2. Overall cost, including tests, medical visits, hospital expenditure and pharmacological treatment, was 420,264,000 pesetas for the entire cohort. The direct annual cost per patient ran at 278,321 pesetas. The cost caused by patients treated with Cefixime on the first exacerbations was 77,365 pesetas less, which was mostly due to less hospital expense. The direct annual cost per patient with CB or COPD is high, above the cost of other chronic respiratory pathologies such as bronchial asthma. There are notably greater hospital costs for CB and COPD, explained by these patients' mean greater age and the non-reversible and progressive deterioration of their respiratory function.
Publisher: Springer Science and Business Media LLC
Date: 09-2012
Publisher: Cambridge University Press (CUP)
Date: 02-2020
DOI: 10.1017/THG.2020.7
Abstract: Reading and language abilities are critical for educational achievement and success in adulthood. Variation in these traits is highly heritable, but the underlying genetic architecture is largely undiscovered. Genetic studies of reading and language skills traditionally focus on children with developmental disorders however, much larger unselected adult s les are available, increasing power to identify associations with specific genetic variants of small effect size. We introduce an Australian adult population cohort (41.7–73.2 years of age, N = 1505) in which we obtained data using validated measures of several aspects of reading and language abilities. We performed genetic association analysis for a reading and spelling composite score, nonword reading (assessing phonological processing: a core component in learning to read), phonetic spelling, self-reported reading impairment and nonword repetition (a marker of language ability). Given the limited power in a s le of this size (~80% power to find a minimum effect size of 0.005), we focused on analyzing candidate genes that have been associated with dyslexia and developmental speech and language disorders in prior studies. In gene-based tests, FOXP2 , a gene implicated in speech/language disorders, was associated with nonword repetition ( p .001), phonetic spelling ( p = .002) and the reading and spelling composite score ( p .001). Gene-set analyses of candidate dyslexia and speech/language disorder genes were not significant. These findings contribute to the assessment of genetic associations in reading and language disorders, crucial for understanding their etiology and informing intervention strategies, and validate the approach of using unselected adult s les for gene discovery in language and reading.
Publisher: Cambridge University Press (CUP)
Date: 21-01-2019
DOI: 10.1017/THG.2018.75
Abstract: We recently reported an association of offspring educational attainment with polygenic risk scores (PRS) computed on parent’s non-transmitted alleles for educational attainment using the second GWAS meta-analysis article on educational attainment published by the Social Science Genetic Association Consortium. Here we test the replication of these findings using a more powerful PRS from the third GWAS meta-analysis article by the Consortium. Each of the key findings of our previous paper is replicated using this improved PRS ( N = 2335 adolescent twins and their genotyped parents). The association of children’s attainment with their own PRS increased substantially with the standardized effect size, moving from β = 0.134, 95% CI = 0.079, 0.188 for EA2, to β = 0.223, 95% CI = 0.169, 0.278, p .001, for EA3. Parent’s PRS again predicted the socioeconomic status (SES) they provided to their offspring and increased from β = 0.201, 95% CI = 0.147, 0.256 to β = 0.286, 95% CI = 0.239, 0.333. Importantly, the PRS for alleles not transmitted to their offspring — therefore acting via the parenting environment — was increased in effect size from β = 0.058, 95% CI = 0.003, 0.114 to β = 0.067, 95% CI = 0.012, 0.122, p = .016. As previously found, this non-transmitted genetic effect was fully accounted for by parental SES. The findings reinforce the conclusion that genetic effects of parenting are substantial, explain approximately one-third the magnitude of an in idual’s own genetic inheritance and are mediated by parental socioeconomic competence.
Publisher: Proceedings of the National Academy of Sciences
Date: 23-08-2022
Abstract: The use of spoken and written language is a fundamental human capacity. In idual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed in idually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in s les of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10 −8 ) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.
Publisher: Springer Science and Business Media LLC
Date: 11-1994
DOI: 10.1007/BF02245346
Publisher: Springer Science and Business Media LLC
Date: 10-11-2010
DOI: 10.1038/MP.2009.120
Abstract: The status of DYX1C1 (C15q21.3) as a susceptibility gene for dyslexia is unclear. We report the association of this gene with reading and spelling ability in a s le of adolescent twins and their siblings. Family-based association analyses were carried out on 13 single-nucleotide polymorphisms (SNPs) in DYX1C1, typed in 790 families with up to 5 offspring and tested on 6 validated measures of lexical processing (irregular word) and grapheme-phoneme decoding (pseudo-word) reading- and spelling-based measures of dyslexia, as well as a short-term memory measure. Significant association was observed at the misssense mutation rs17819126 for all reading measures and for spelling of lexical processing words, and at rs3743204 for both irregular and nonword reading. Verbal short-term memory was associated with rs685935. Support for association was not found at rs3743205 and rs61761345 as previously reported by Taipale et al., but these SNPs had very low (0.002 for rs3743205) minor allele frequencies in this s le. These results suggest that DYX1C1 influences reading and spelling ability with additional effects on short-term information storage or rehearsal. Missense mutation rs17819126 is a potential functional basis for the association of DYX1C1 with dyslexia.
Publisher: Oxford University Press (OUP)
Date: 12-01-2007
DOI: 10.1093/HMG/DDL487
Abstract: Recent studies have made great strides towards identifying putative genetic events underlying the evolution of the human brain and its emergent cognitive capacities. One of the most intriguing findings is the recurrent identification of adaptive evolution in genes associated with primary microcephaly, a developmental disorder characterized by severe reduction in brain size and intelligence, reminiscent of the early hominid condition. This has led to the hypothesis that the adaptive evolution of these genes has contributed to the emergence of modern human cognition. As with other candidate loci, however, this hypothesis remains speculative due to the current lack of methodologies for characterizing the evolutionary function of these genes in humans. Two primary microcephaly genes, ASPM and Microcephalin, have been implicated not only in the adaptive evolution of the lineage leading to humans, but in ongoing selective sweeps in modern humans as well. The presence of both the putatively adaptive and neutral alleles at these loci provides a unique opportunity for using normal trait variation within humans to test the hypothesis that the recent selective sweeps are driven by an advantage in cognitive abilities. Here, we report a large-scale association study between the adaptive alleles of these genes and normal variation in several measures of IQ. Five independent s les were used, totaling 2393 subjects, including both family-based and population-based datasets. Our overall findings do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ. As we enter the post-genomic era, with the number of candidate loci underlying human evolution growing rapidly, our findings highlight the importance of direct experimental validation in elucidating their evolutionary role in shaping the human phenotype.
Publisher: Informa UK Limited
Date: 2003
Publisher: Elsevier BV
Date: 08-2013
Publisher: Wiley
Date: 29-08-2014
DOI: 10.1111/GBB.12158
Publisher: Springer Science and Business Media LLC
Date: 24-07-2008
Publisher: Elsevier BV
Date: 10-2007
DOI: 10.1016/J.BIOPSYCH.2007.03.007
Abstract: KIAA0319 (6p22.2) has recently been implicated as a susceptibility gene for dyslexia. We aimed to find further support for this gene by examining its association with reading and spelling ability in adolescent twins and their siblings unselected for dyslexia. Ten single nucleotide polymorphisms (SNPs) in or near the KIAA0319 gene were typed in 440 families with up to five offspring who had been tested on reading and spelling tasks. Family-based association analyses were performed, including a univariate analysis of the principal component reading and spelling score derived from the Components of Reading Examination (CORE) test battery and a bivariate analysis of whole-word reading tests measured in a slightly larger s le. Significant association with rs2143340 (TTRAP) and rs6935076 (KIAA0319) and with a three-SNP haplotype spanning KIAA0319 and TTRAP was observed. The association with rs2143340 was found in both analyses, although the effect was in the opposite direction to that previously reported. The effect of rs6935076 on the principal component was in the same direction as past findings. Two of the three significant in idual haplotypes showed effects in the opposite direction to the two prior reports. These results suggest that a multilocus effect in or near KIAA0319 may influence variation in reading ability.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2009
DOI: 10.1007/S10519-009-9275-Y
Abstract: The Author Recognition Test (ART) measures print exposure and is a unique predictor of phonological and orthographic processes in reading. In a s le of adolescent and young adult twins and siblings (216 MZ/430 DZ pairs, 307 singletons aged 11-29 years) ART scores were moderately heritable (67%) and correlated with reading and verbal abilities, with genes largely accounting for the covariance. We also examine whether high (and low) (i.e. 1SD above the mean) represents a quantitative extreme of the normal distribution. Heritability for high ART was of similar magnitude to the full s le, but, a specific genetic factor, independent from both low ART performance and high reading ability, accounted for 53-58% of the variance. This suggests a distinct genetic etiology for high ART ability and we speculate that the specific genetic influence is on orthographical processing, a critical factor in developing word recognition skills.
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.JAAC.2010.10.010
Abstract: Breast-fed C-allele carriers of the rs174575 single nucleotide polymorphism in the fatty acyl desaturase 2 (FADS2) gene have been reported to show a 6.4 to 7 IQ point advantage over formula-fed C-allele carriers, with no effect of breast-feeding in GG carriers. An Australian s le was examined to determine if an interaction between breast-feeding and the rs174575 single nucleotide polymorphism had any effect on IQ. This hypothesis was tested in more than 700 families of adolescent twins assessed for IQ and breast-feeding, birth weight, and FADS2 polymorphisms, and parental socioeconomic status and education, and maternal FADS2 status. No significant evidence for a moderating effect on IQ of rs174575 C-carrier status and breast-feeding was found, and there no effects of maternal FADS2 status on offspring IQ. In addition, no main effects of any FADS2 polymorphisms on IQ were found when the genotype was kept as two-homozygote and one-heterozygote categories and indeed no evidence for effects of breast-feeding on IQ scores after controlling for parental socioeconomic status and education. The investigation was extended to two additional FADS2 polymorphisms (rs1535 and rs174583), but again, although these polymorphisms code alleles affecting fatty acid metabolism, no main or interaction effects were found on IQ. These results support the view that apparent effects of breast-feeding on IQ reflect differential likelihood of breast-feeding as a function of parental education and did not support the predicted interaction effect of FADS2 and breast-feeding on IQ.
Publisher: The Royal Society
Date: 22-10-2003
Publisher: Springer Science and Business Media LLC
Date: 13-01-2010
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.NEULET.2009.04.050
Abstract: We report on the association of KIBRA with memory in two s les of older in iduals assessed on either memory for semantically unrelated word stimuli (Rey Auditory Verbal Learning Test, n=2091), or a measure of semantically related material (the WAIS Logical Memory Test of prose-passage recall, n=542). SNP rs17070145 was associated with delayed recall of semantically unrelated items, but not with immediate recall for these stimuli, nor with either immediate or delayed recall for semantically related material. The pattern of results suggests a role for the T-->C substitution in intron 9 of KIBRA in a component of episodic memory involved in long-term storage but independent of processes shared with immediate recall such as rehearsal involved in acquisition and rehearsal or processes.
Publisher: Wiley
Date: 03-2009
Publisher: Elsevier BV
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 18-07-2007
Publisher: Cold Spring Harbor Laboratory
Date: 04-11-2021
DOI: 10.1101/2021.11.04.466897
Abstract: The use of spoken and written language is a capacity that is unique to humans. In idual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30-80%, depending on the trait. The relevant genetic architecture is complex, heterogeneous, and multifactorial, and yet to be investigated with well-powered studies. Here, we present a multicohort genome-wide association study (GWAS) of five traits assessed in idually using psychometric measures: word reading, nonword reading, spelling, phoneme awareness, and nonword repetition, with total s le sizes ranging from 13,633 to 33,959 participants aged 5-26 years (12,411 to 27,180 for those with European ancestry, defined by principal component analyses). We identified a genome-wide significant association with word reading (rs11208009, p=1.098 × 10 −8 ) independent of known loci associated with intelligence or educational attainment. All five reading-/language-related traits had robust SNP-heritability estimates (0.13–0.26), and genetic correlations between them were modest to high. Using genomic structural equation modelling, we found evidence for a shared genetic factor explaining the majority of variation in word and nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence and educational attainment. A multivariate GWAS was performed to jointly analyse word and nonword reading, spelling, and phoneme awareness, maximizing power for follow-up investigation. Genetic correlation analysis of multivariate GWAS results with neuroimaging traits identified association with cortical surface area of the banks of the left superior temporal sulcus, a brain region with known links to processing of spoken and written language. Analysis of evolutionary annotations on the lineage that led to modern humans showed enriched heritability in regions depleted of Neanderthal variants. Together, these results provide new avenues for deciphering the biological underpinnings of these uniquely human traits.
Publisher: Elsevier BV
Date: 02-2008
Publisher: Elsevier BV
Date: 05-2001
Publisher: Springer Science and Business Media LLC
Date: 20-10-2022
DOI: 10.1038/S41588-022-01192-Y
Abstract: Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia.
Publisher: Cambridge University Press (CUP)
Date: 02-2023
DOI: 10.1017/THG.2023.2
Abstract: Reading difficulties are prevalent worldwide, including in economically developed countries, and are associated with low academic achievement and unemployment. Longitudinal studies have identified several early childhood predictors of reading ability, but studies frequently lack genotype data that would enable testing of predictors with heritable influences. The National Child Development Study (NCDS) is a UK birth cohort study containing direct reading skill variables at every data collection wave from age 7 years through to adulthood with a subs le (final n = 6431) for whom modern genotype data are available. It is one of the longest running UK cohort studies for which genotyped data are currently available and is a rich dataset with excellent potential for future phenotypic and gene-by-environment interaction studies in reading. Here, we carry out imputation of the genotype data to the Haplotype Reference Panel, an updated reference panel that offers greater imputation quality. Guiding phenotype choice, we report a principal components analysis of nine reading variables, yielding a composite measure of reading ability in the genotyped s le. We include recommendations for use of composite scores and the most reliable variables for use during childhood when conducting longitudinal, genetically sensitive analyses of reading ability.
Publisher: Springer Science and Business Media LLC
Date: 07-1995
DOI: 10.1007/BF02246195
Abstract: It is estimated that women with CKD are ten times more likely to develop preecl sia than women without CKD, with preecl sia affecting up to 40% of pregnancies in women with CKD. However, the shared phenotype of hypertension, proteinuria, and impaired excretory kidney function complicates the diagnosis of superimposed preecl sia in women with CKD who have hypertension and/or proteinuria that predates pregnancy. This article outlines the diagnoses of preecl sia and superimposed preecl sia. It discusses the pathogenesis of preecl sia, including abnormal placentation and angiogenic dysfunction. The clinical use of angiogenic markers as diagnostic adjuncts for women with suspected preecl sia is described, and the limited data on the use of these markers in women with CKD are presented. The role of kidney biopsy in pregnancy is examined. The management of preecl sia is outlined, including important advances and controversies in aspirin prophylaxis, BP treatment targets, and the timing of delivery.
Publisher: Elsevier BV
Date: 05-2016
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Timothy Bates.