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Vous consultezGenetic bases of developmental dyslexia: A capsule review of heritability estimates
AuteurElena L. Grigorenko  Yale University, USA & Moscow State University,...
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In one of the early reports to the scientific community on the state of schooling in the United Kingdom, James Kerr (1897) raised, among many important issues, the issue of educating children with special needs. Of note is the following citation: “But besides the generally dull there are mentally exceptional, many quite suitable for ordinary school provided the teacher knows their peculiarities. Almost unique cases are found with most bizarre defects.” Kerr continues on with a description of these defects, among which he mentions “...a boy with word blindness, who can spell the separate letters...” He then mentions that it appears that in such defects “heredity places a considerable part...” (Kerr, Here and above, p. 668).
2 Now, almost 110 years later, the concept of “word blindness” has been replaced with that of developmental dyslexia or specific reading disability. Kerr’s insight, however, remains quite accurate with regard to the componential structure of deficits (e.g., probands can spell letters, but cannot put words together) and the role of heredity in the manifestation of developmental dyslexia. Noticeably, 110 years of research have allowed the field to unfold Kerr’s general statements, support them with convincing data, and offer specific interpretations of his early ideas regarding the componential profile of this deficit and the role of heredity in its etiology.
3 This article briefly reviews the studies attesting to the “considerable” role of heritable factors in the developmental dyslexia (DD). Here DD is viewed both holistically and through a constellation of separate, although correlated, cognitive processes. Defined holistically, dyslexia is a difficulty in mastering reading despite access to instruction adequate for a typically developing child (Olson, 2002). Defined componentially, dyslexia is a difficulty (or set of difficulties) with one or more of the following skills: (a) reading single words of different length, difficulty, familiarity, and frequency (i.e., single-word reading difficulty); (b) decoding, parsing, and sounding out unfamiliar or nonsense words into smaller phonologically recognizable units (i.e., phonological decoding difficulty); (c) identifying irregular words that violate standard rules of letter-sound correspondence (i.e., orthographical coding difficulty); (d) speeded retrieval of names of simple familiar objects, words, colors, and digits (i.e., rapid naming difficulty); (e) spelling single words of different length, difficulty, familiarity, and frequency (i.e., spelling difficulty); and/or (f) manipulating phonemes, which are elementary meaningful units of spoken language (i.e., phonemic difficulty). Of note is that in typically developing children, the correlations between these componential processes are substantial, indicating that good single-word readers tend to be good decoders as well as good namers and so forth, irrespective of their general cognitive ability (Shatil & Share, 2003). However, individuals with dyslexia can show dramatic mismatches between different components of their skill profiles (Vellutino, Fletcher, Snowling, & Scanlon, 2004).
4 This review is aimed at providing a summary of the literature regarding the estimates of the role of heritability in the manifestation of developmental dyslexia defined both holistically and componentially. To achieve this aim, first, different twin samples around the world contributing to this literature are introduced. Second, relevant summative information from these samples is presented. Third, a meta-analysis of estimated genetic and environmental effects on dyslexia and reading-related componential process is conducted. Finally, the implications of these findings for genetic studies of developmental dyslexia are discussed.
5 The heritable nature of DD and reading problems was first demonstrated in the first half of this century (Kagen, 1943; Norrie, 1939; Orton, 1937; Thomas, 1905). However, the first quantification of heritability was provided through twin studies and resulted in rather high estimates of its role. The very first twin pairs with dyslexia studied by Bertil Hallgren (3 identical or monozygotic, MZ, and 3 fraternal, or dizygotic, DZ, pairs), Edith Norrie (7 MZ and 21 DZ), and Knud Hermann (1 MZ and 3 DZ) (Hermann, 1956), presented concordance ratios of 1 and .33 for MZ and DZ twins correspondingly. Later concordance rates for MZ and DZ twins, although variable and biased upward by then-available ascertainment schemes, have consistently supported this first indication of the substantial contribution of genes in the manifestation of reading problems. Specifically, MZ and DZ concordance rates were reported as 100% and 34% (Weinschenk, 1965), 100% and 35% (Zerbin-Rüdin, 1967), and 83% and 29% (Bakwin, 1973), respectively. As it is often the case in science, however, many of these estimates have been revised by the data generated through studies with better designs, larger numbers of participants, and theory-driven approaches to DD. Many of these improved estimates were initially introduced to the literature in the 1980s (DeFries, Fulker, & LaBuda, 1987; Olson, Wise, Conners, Rack, & Fulker, 1989; Stevenson, 1991; Stevenson, Graham, Fredman, & McLoughlin, 1987), quantifying the magnitude of genetic control with precision. Yet, the latest studies, published only recently, provide the field with the state-of-the-art estimates of heritability of DD and related deficits. Here these studies are briefly reviewed and meta-analyzed.
6 The data collected by researchers at the CLDRC have contributed to a number of relevant publications. A brief intellectual history of the CLDRC is presented in Olson (2002). The CLDRC primarily recruited identical and fraternal twins aged 8 to 18 through Colorado school districts, using a multi-step process. First, all twin pairs were identified in a given school or school district. Second, twin pairs in which at least one of the twins had a school history of reading problems were invited for extensive assessment. Only participants whose verbal or verbal and performance IQ met the threshold established by the researchers were included in this sample. Other inclusion criteria assumed English as the twins’ native language and an absence of serious neurological, emotional, behavioral, or any uncorrected visual or auditory acuity problems. Third, a comparison group matched to the RD-history group in age, gender, and school district, but free of reading problems, was ascertained. Fourth, after the assessments were administered and the data processed, a phenotype-specific sample of affected individuals was identified within the RD-history sample. Specifically, this sample included only the participants who scored 1.5 sd below the mean of the comparison group in the relevant assessment.
7 The contribution of the CLDRC is difficult to estimate because most of the field’s estimates of the magnitude of heritability of DD and reading-related processes are derived from this dataset. Here, only three publications from this group (Davis et al., 2001; Gayá n & Olson, 2001, 2003) are meta-analyzed (see Table 1). These publications were selected either because they have the most nearly complete sample presented or because they deal with non-overlapping phenotypes. However, the Discussion briefly reviews a number of lines of investigation conducted at the CLDRC. Specifically, the Discussion reviews the CLDRC researchers’ contributions to the evaluation of genetic correlations between various reading-related processes and the role of a number of important moderating variables whose influence might differentiate heritability estimates (e.g., IQ, gender, and age).
8 Recently, the CLDRC researchers launched an international project where young twins are evaluated not only in the US, but also in Australia and Norway (Byrne, Delaland, Fielding-Barnsley, & Quain, 2002). The overall purpose of this work it to observe the developmental trajectory of mastery of reading (Kindergarten, first, and second grades) and to parse out the components of this trajectory into those controlled by genes and those controlled by environment. At this point, only the data from Kindergarten are available. To generate these data, children of approximately 5 years of age were tested in their home or preschools during a 5-day assessment session (see Table 1).
9 The 1987 sample (Stevenson et al., 1987) included 285 samples of adolescent twins. These adolescents were recruited through their hospital records at the time of birth and through the Inner London primary schools. The testing was carried out at the twins’ homes.
10 The 1999 sample was built using a cross-sectional design recruiting from younger (5 years old) and older (7 years old) cohorts of English-speaking children in the London area (Hohnen & Stevenson, 1999). The families of twins were initially contacted through schools attended by the children. If the family responded positively, the researchers established a direct connection with the family and scheduled an evaluation. The children were tested at their homes with a large battery of literary, language, reading skills, and general ability assessments (see Table 1).
11 TEDS is a longitudinal population-based study of twins born in England and Wales in 1994 and 1995 (Trouton, Spinath, & Plomin, 2002). The families were contacted when the twins were abot a year old, after being screened for infant mortality. Of the 11,350 families registered as having twins, 10,932 (96.3%) returned informed consents. Subsequently, a letter describing the project was sent to the families and a postcard was included so that the families could indicate their interest in participating by returning the postcard to investigators. The responding parents then received booklets for data collection, which contained parent-based assessments on language and nonverbal development at 2, 3, and 4 years. At the age of 7, when the children entered their first grade at school, the families were contacted again. The ag-–7 booklet contained assessments of word reading and vocabulary, which were then administered to the children over the phone. In addition, children’s teachers were contacted and the teacher ratings of the children’s performance in English and math were collected. The exclusion criteria included inconclusive zygosity assignment, serious medical conditions, and native language other than English. The sample sizes of twins available through the TEDS for analyses vary from year to year of data collection, but amount to thousands of pairs of twins. Here (see Table 1), only the data from the collection carried out when the twins were 7 years old is presented (Harlaar, Spinath, Dale, & Plomin, 2004).
12 As indicated above, this report does not claim do be an exhaustive meta-analysis of all published work on heritability of DD or reading skills. On the contrary, the point here is to review the latest and largest samples that provided heritability estimates not only for the holistic phenotypes of DD, but also for componential processes of reading. To achieve this objective, all relevant estimates were summarized in Table 1. Correspondingly, Table 1 provides estimates of heritability, or the proportion of variance accounted for by genetic factors (h2), as well as estimates of the proportions of variance accounted for by shared (c2) and non-shared (e2) environment.
13 In this meta-analysis, the weighted means h2,c2, and e2 were estimated to consider the sample size. Specifically, following Li and colleagues (Li, Cheng, Ma, & Swan, 2003), we adopted the weighting formula presented by Sutton et al. (Sutton, Abrams, Jones, Sheldon, & Song, 2000):
14 Here k is the number of studies, ni is the corresponding sample size for the ith study (i=1, ... k), is the mean heritability, and is the reportedheritability for the ith study.
15 The corresponding conditional variance is:
16 These calculations were performed for specific phenotypes, as well as for the so-called “Averaged Estimates,” when all reading-related phenotypes (shown in italics in Table 1) were collapsed into a single indicator.
17 The results of the meta-analysis are presented in Table 2 and Figure 1. The inspection of the results in Table 2 and Figure 1 permits the formulation of the following statements. First, it is quite apparent that the driving force underlying individual variation in reading is genetic, whether heritability is estimated in unselected (i.e., covering an unrestricted range of abilities) or selected (i.e., including participants ascertained through individuals whose performance on reading-related assessments is that below of a certain threshold) samples. Analyzed together, these latest twin studies attest to the substantiality of the role of genetic factors in reading: when error variance is taken into account, these factors control anywhere between 41 to 74% of the variance (see Averaged Estimate). This figure appears to be even higher when specific reading skills are taken into account; thus, genetic control in spelling might account for as much as 90% of the variance !
18 Second, when environmental factors considered, there appears to be a substantial contribution of shared environment to the etiology of individual differences in reading. These contributions appear to be estimated with the smallest error, thus indicating that these estimates are quite consistent from study to study. When reading is considered holistically (i.e., all process contributing to reading are co-analyzed), the contribution of shared environment is estimated at 30%.
19 Third, the meta-analysis revealed that the estimates of non-shared environment are, collectively, unreliable. They appear to be fluctuating somewhere around 10% and they contain much error in them. Fourth, when h2, c2, e2 are considered separately for distinct reading-related processes (Word Recognition, Spelling, and Phonemic Awareness), they do not statistically differ from each other. Finally, the heritability estimates obtained in unselected samples appear to be uniformally and statistically significantly higher than those obtained in selected samples.
20 Once again, the evidence from the latest twin studies of the etiology of individual differences in reading and reading-related processes is abundantly clear—there is a strong genetic factor or a constellation of factors that influence both the success of the mastery of reading skill and variation
21 in performance on reading-related assessments. Thus, what was initially just hypothesized by Kerr has now been demonstrated abundantly in multiple studies in different samples. However, whereas the statement of the importance of genetic control has been heard before, this meta-analysis provides the most up-to-date support of this assertion by illustrating it with estimates obtained through a set of multiple powerful studies of twins. Putting the results of this meta-analysis into the larger context of research on genetic factors contributing to the etiology of DD and componential processes of reading, a number of issues should be mentioned.
22 First, it is well known that componential processes substantially correlate with each other and with the holistic definition of DD. Although, as illustrated in Table 1, there is a substantial variability in heritability estimates of specific reading-related processes across different samples, in this meta-analysis the summative process-specific heritability estimates are not statistically distinguishable from each other. Of interest here, then, is obtaining estimates of genetic (latent) correlations between these components. These analyses were conducted by researchers from the CDLRC (Davis et al., 2001; Gayá n & Olson, 2001, 2003). These so-called bivariate analyses, which permit an estimation of the genetic correlation indicative of an overlap in genetic variance between different traits, produced interesting results. Specifically, genetic correlations between reading-related processes range from .45 (95% CI .42–.70) for Phonemic Awareness and Orthographic Coding to .97 (95% CI .93–1.00) for Phonological Decoding and Word Recognition (Gayá n & Olson, 2003). Davis et al. (2001) reported bivariate heritability estimates for Phonological Decoding, Orthographic Choice, Discriminant Function, and Speed of Naming, and also stated that results suggested the presence of substantial genetic correlations between reading-related componential processes. However, the magnitude of genetic overlap reported by Davis et al. (2001) was significantly lower than that reported by Gayá n & Olson (2003). Similar attempts to estimate the genetic overlap between different indicators of reading have been carried out on samples of siblings and their families (Marlow et al., 2001) and nuclear families (Wijsman et al., 2000). Once again, these studies clearly illustrated the presence of shared genetic variance, and, therefore, shared genes between various genetic components. However, the magnitude of this “sharedness” varies, depending on the sample and method with which it is estimated. For example, while Marlow and colleagues suggest that there is a general “reading” factor that is characterized by high familiality (.68 ± .16) and, presumably, high heritability, Wijsman and colleagues suggest that, although possibly overlapping in the presence of major genes, components of reading appear to be controlled by genes unique to some or each of these processes. This question of what these “shared” and “unique” genes are appears to be one of the most intriguing unresolved questions in the field of genetic studies of DD and reading-related processes.
23 In 2003, the first candidate gene for DD, a gene called EKN1, was discovered through analyses of a family and a set of individuals in Finland with dyslexia (Taipale et al., 2003). A number of investigators have started the examination of the role of this gene in different samples across the world, but no replications have been reported so far. It is possible that EKN1 is one of the “shared” dyslexia genes—a gene that contributes to all reading-related phenotypes in all samples. It is also possible that EKN1 contributes to only particular aspects of dyslexia; specifically, the Finnish family in which this gene co-segregates with dyslexia is characterized by pronounced spelling difficulties. Yet another possibility is that EKN1 is specific to the Finnish sample and, given that DD is genetically a heterogeneous condition, it will not be seen as a DD-related factor in other samples around the world. Both of these possibilities have to be investigated further before we know the answer to these questions.
24 Currently, there are eight regions of interest in the genome that are being actively pursued by different research groups as areas potentially harboring genes involved in dyslexia or reading-related processes (Grigorenko, in press). These regions are located on chromosomes 1 (short arm), 2 (short arm), 3 (centromeric region), 6 (both short and long arms), 11 (short arm), 15 (long arm), and 18 (short arm). All of these genes might contribute to all DD-related phenotypes or only to some of them. As has been also pointed out, they might be of importance in all populations or only in some of them (e.g., for DD among Russians, but not among Japanese or the other way around).
25 Second, it is important to mention here that researchers have investigated the role of a number of moderating factors differentiating the estimates of heritability. These factors are age (Pennington, Gilger, Olson, & DeFries, 1992), gender (Wadsworth, DeFries, Stevenson, Gilger, & Pennington, 1992), and IQ (Knopik et al., 2002). A limitation of this meta-analysis is that it does not address the role of mediating factors. There is a reason for this limitation—the data themselves at this point do not provide enough information to address the role of these mediators in the context of meta-analytic comparisons. Yet, even a simply eye-balling of the data presented in Table 1 suggests that both age and gender might be important “third-variable” factors mediating the pathways between the genome and behavioral manifestation of DD.
26 All in all, there is much to do in order to decipher the genetic mechanism of DD. Yet, something is really clear—there is substantial genetic contribution to DD and reading-related process and all the efforts that are currently going into this work will sooner or later pay off!
27 Author Note. — Preparation of this essay was supported by Grant REC-9979843 from the National Science Foundation and by a grant under the Javits Act Program (Grant No. R206R00001) as administered by the Institute for Educational Sciences, US Department of Education. Grantees undertaking such projects are encouraged to express freely their professional judgment. This article, therefore, does not necessarily represent the position or policies of the NSF, the Institute for Educational Sciences, or the US. Department of Education, and no official endorsement should be inferred. I express my gratitude to Mrs. Robyn Rissman for her editorial assistance.
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[ 1] Yale University, USA & Moscow State University, Russia. Yale University, PACE Center, 340 Edwards Street, PO Box 208358, New Haven, CT 06520-8358 (firstname.lastname@example.org).
Cette brève revue vise à fournir un résumé de la littérature relative à l’estimation du rôle que joue l’héritabilité dans la manifestation de la dyslexie développementale définie de manière à la fois holistique et componentielle. Dans cette perspective, nous présenterons dans un premier temps différents échantillons de jumeaux qui apportent une contribution à cette littérature. Notre discussion commence par un retour aux idées du siècle dernier ayant ouvert la voie à l’hypothèse de la nature familiale de la dyslexie. Elle continue par une évocation des premières études de jumeaux qui ont initialement confirmé cette hypothèse. Elle commente brièvement les travaux publiés dans les années 1980 et le début des années 1990 ayant amélioré certaines de ces estimations. Elle exploite la revue des études de jumeaux plus récentes, au design plus soigneux, avec leurs tailles d’échantillon élevées. Dans un deuxième temps, les informations récapitulatives pertinentes de ces échantillons sont présentées. Plus spécifiquement, les échantillons collectés dans le Centre de recherche des troubles de l’apprentissage du Colorado, dans les Études de jumeaux de Londres et dans les Études du développement précoce des jumeaux de Grande-Bretagne sont décrits, en incluant la distribution en âge et en genre des participants, le schéma de recrutement et les phénotypes évalués. En troisième lieu, une méta-analyse des effets génétiques et environnementaux estimés sur la dyslexie et sur les processus componentiels relatifs à la lecture est effectuée. La méthode de cette méta-analyse est spécifiée et les données qui ont été entrées dans ces analyses sont présentées. Les résultats de cette méta-analyse sont résumés, indiquant :1 / une confirmation supplémentaire du fait bien établi que l’étiologie à la fois des différences individuelles dans les processus relatifs à la lecture et de l’échec de la maîtrise de la lecture (que l’on appelle généralement dyslexie ou trouble spécifique de la lecture) est principalement contrôlée par des facteurs génétiques ; 2 / l’importance de la contribution des facteurs génétiques au travers de tous les processus liés à la lecture (par ex. la conscience phonologique, l’orthographe et la lecture de mots isolés) ; 3 / le rôle considérable, bien que quelque peu moindre comparativement, de l’environnement partagé dans l’étiologie des différences individuelles en lecture et de la dyslexie développementale ; et 4 / l’absence de preuve pour ce qui est du rôle de l’environnement non partagé. Enfin, les implications de ces résultats pour les études génétiques de la dyslexie développementale en cours sont discutées. Plus spécifiquement, la discussion évoque brièvement la nécessité de prendre en considération à la fois les phénotypes componentiels et holistiques de la dyslexie développementale; fait une revue du statut de la recherche en génétique moléculaire; et propose quelques commentaires sur l’importance de la prise en considération de facteurs modérateurs (par ex. l’âge, le genre et le QI) dans les investigations de l’étiologie des problèmes et des différences individuelles en lecture.
Mots clesProcessus componentiels de lecture, Dyslexie développementale, Héritabilité
This brief review is aimed at providing a summary of the literature regarding the estimates of the role heritability plays in the manifestation of developmental dyslexia defined both holistically and componentially. To achieve this aim, first, different twin samples around the world contributing to this literature are introduced. Second, relevant summative information from these samples is presented. Third, a meta-analysis of estimated genetic and environmental effects on dyslexia and reading-related componential process is conducted. Finally, the implications of these findings for ongoing genetic studies of developmental dyslexia are discussed.
Mots clesComponential processes of reading, Developmental dyslexia, Heritability
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POUR CITER CET ARTICLE
Elena L. Grigorenko « Genetic bases of developmental dyslexia: A capsule review of heritability estimates », Enfance 3/2004 (Vol. 56), p. 273-288.
URL : www.cairn.info/revue-enfance-2004-3-page-273.htm.
DOI : 10.3917/enf.563.0273.