Pleiotropic Effects of DCDC2 and DYX1C1 Genes on Language and Mathematics Traits in Nuclear Families of Developmental Dyslexia

Marino, Cecilia; Mascheretti, Sara; Riva,; Cattaneo, Francesca; Rigoletto, C.; Rusconi, Marianna; Gruen, Jeffrey R.; Giorda, Roberto; Lazazzera, Claudio; Molteni, Massimo

doi:10.1007/s10519-010-9412-7

Cited by 43 publications

(32 citation statements)

References 48 publications

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“…Phenotypic and genotypic data were available for 804 offspring belonging to 493 unrelated Italian nuclear families of probands with DD, all of which have already participated in our previous association studies on these candidate genes (Marino et al 2003(Marino et al , 2004(Marino et al , 2005(Marino et al , 2007(Marino et al , 2011(Marino et al , 2012Mascheretti et al 2014a, b). Reading was available for 612 offspring, spelling for 579 offspring, memory letters for 355 offspring and memory digits for 480 offspring.…”

Section: Resultsmentioning

confidence: 99%

“…This study is based on an ongoing project on the genetic basis of DD (Marino et al 2003(Marino et al , 2004(Marino et al , 2005(Marino et al , 2007(Marino et al , 2011(Marino et al , 2012Mascheretti et al 2014a, b). The ascertainment scheme has been reported in detail elsewhere (Marino et al 2003).…”

Section: Samplementioning

confidence: 99%

“…Among the above-mentioned genes, seven DD candidate genes have been replicated in at least one independent sample, i.e., DYX1C1, DCDC2, KIAA0319, C2ORF3, MRPL19, ROBO1, and GRIN2B (Ludwig et al 2009;Scerri and Schulte-Körne 2010;Couto et al 2010;Lim et al 2011;Kirsten et al 2012;Marino et al 2012;Powers et al 2013;Venkatesh et al 2013Venkatesh et al , 2014Mascheretti et al 2014a, b;Tran et al 2014). We previously reported the association of single nucleotide polymorphisms (SNPs) spanning the DYX1C1, DCDC2, KIAA0319, ROBO1, and GRIN2B genes with DD and DD-related quantitative traits in affected Italian nuclear families (Marino et al 2007(Marino et al , 2011(Marino et al , 2012Mascheretti et al 2014a, b). At the biochemical and cell biological functions level, these genes play a role in neuronal migration during the embryonal period, in ciliary function and in neuronal pattern formation (Akashi et al 2009;Kere 2014).…”

Section: Introductionmentioning

confidence: 99%

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An assessment of gene-by-gene interactions as a tool to unfold missing heritability in dyslexia

et al. 2015

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Even if substantial heritability has been reported and candidate genes have been identified extensively, all known marker associations explain only a small proportion of the phenotypic variance of developmental dyslexia (DD) and related quantitative phenotypes. Gene-by-gene interaction (also known as "epistasis"--G × G) triggers a non-additive effect of genes at different loci and should be taken into account in explaining part of the missing heritability of this complex trait. We assessed potential G × G interactions among five DD candidate genes, i.e., DYX1C1, DCDC2, KIAA0319, ROBO1, and GRIN2B, upon DD-related neuropsychological phenotypes in 493 nuclear families with DD, by implementing two complementary regression-based approaches: (1) a general linear model equation whereby the trait is predicted by the main effect of the number of rare alleles of the two genes and by the effect of the interaction between them, and (2) a family-based association test to detect G × G interactions between two unlinked markers by splitting up the association effect into a between- and a within-family genetic orthogonal components. After applying 500,000 permutations and correcting for multiple testing, both methods show that G × G effects between markers within the DYX1C1, KIAA0319/TTRAP, and GRIN2B genes lower the memory letters composite z-score of on average 0.55 standard deviation. We provided initial evidence that the effects of familial transmission of synergistic interactions between genetic risk variants can be exploited in the study of the etiology of DD, explain part of its missing heritability, and assist in designing customized charts of individualized neurocognitive impairments in complex disorders, such as DD.

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Section: Resultsmentioning

confidence: 99%

Section: Samplementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An assessment of gene-by-gene interactions as a tool to unfold missing heritability in dyslexia

et al. 2015

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“…Recent studies have suggested that comprehension involves the automatic and unconscious simulation of past experiences, relying on the processing of sensorimotor representations (see for instance Bergen et al, 2007;Marino et al 2011). According to this "simulation hypothesis", when we understand the meaning of an action-related verb, we unconsciously and automatically simulate the experience of the action described by the verb (Bergen et al, 2007;Barsalou, 1999 Tettamanti et al (2005) observed in a fMRI study the activation during the processing of action-related sentences of the cortical circuit responsible for the planning and execution of the same actions (observationexecution matching system, i.e.…”

Section: Introductionmentioning

confidence: 99%

Reading approach to improve strenght: an explorative study

Lovecchio

Vago

Tornaghi

et al. 2016

jhse

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Many studies and common practice use different load and recovery time combinations to obtain improvements in strength performance. The cross education and speech neurons theory could lead to new strategies in motor skills learning and in fitness improvement. Thus, the aim of this study was to verify if a process similar to cross education and visual phenomenon (reading approach) could improve the strength performance. The study consisted of three matched samples that followed three different protocols (strength training, mental and reading approach) and a control group. After 12 training sessions the improvements in maximal voluntary handgrip were assessed. On average, the improvement in handgrip performance was 3.02, 2.97, 2.07, 1.16 kg for strength, mental, reading and control sample respectively. Significant differences among groups were found while no differences were found before and after the protocol, as well as for the interaction. The post hoc analysis revealed significant differences between the strength sample (after training value) and the control group (before the training). Mental or reading training resulted in almost similar improvements that are close to strength training gains. Indeed, at least for the initial training session, the reading training was broadly similar to well-know protocol and could be used to provide complementary stimulus.

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“…Contrary to nonrandom ascertainment, under random ascertainment, all families including those with no affected member are recruited with probability of unity. It is fundamental to this article that non-random ascertainment has important effects on the structure of an ascertained subpopulation [15][16][17]. Obviously, it introduces classical ascertainment bias [9,10,18].…”

Section: Introductionmentioning

confidence: 99%

Analysis of bivariate binary data with possible chances of wrong ascertainment

Roy

Sarkar

Das

2012

Journal of Statistical Computation and Simulation

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In familial data, ascertainment correction is often necessary to decipher genetic bases of complex human diseases. This is because families usually are not drawn at random or are not selected according to welldefined rules. While there has been much progress in identifying genes associated with a certain phenotype, little attention has been paid so far for familial studies on exploring common genetic influences on different phenotypes of interest. In this study, we develop a powerful bivariate analytical approach that can be used for a complex situation with paired binary traits. In addition, our model has been framed to accommodate the possibility of imperfect diagnosis as traits may be wrongly observed. Thus, the primary focus is to see whether a particular gene jointly influences both phenotypes. We examine the plausibility of this theory in a sample of families ascertained on the basis of at least one affected individual. We propose a bivariate binary mixed model that provides a novel and flexible way to account for wrong ascertainment in families collected with multiple cases. A hierarchical Bayesian analysis using Markov Chain Monte Carlo (MCMC) method has been carried out to investigate the effect of covariates on the disease status. Results based on simulated data indicate that estimates of the parameters are biased when classification errors and/or ascertainment are ignored.

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Pleiotropic Effects of DCDC2 and DYX1C1 Genes on Language and Mathematics Traits in Nuclear Families of Developmental Dyslexia

Cited by 43 publications

References 48 publications

An assessment of gene-by-gene interactions as a tool to unfold missing heritability in dyslexia

An assessment of gene-by-gene interactions as a tool to unfold missing heritability in dyslexia

Reading approach to improve strenght: an explorative study

Analysis of bivariate binary data with possible chances of wrong ascertainment

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