Supplementary Information 1

Materials and Methods

Sample

The battery of test included the following neuropsychological tasks:

1. Text Reading: ‘‘Prove di rapidità e correttezza nella lettura del gruppo MT’’ (‘‘Test for speed and accuracy in reading, developed by the MT group’’)1-2, a text reading task meant to assess reading abilities for meaningful material. It provides separate scores for speed and accuracy. Texts increase in complexity with grade level. Norms are provided for each text.

2. Single word/non-word reading: ‘‘Batteria per la Valutazione della Dislessia e Disortografia volutiva’’ (“Battery for the assessment of developmental reading and spelling disorders”)3. This test assesses speed and accuracy (expressed as the number of errors) in reading word lists (four lists of 24 words) and non-word lists (three lists of 16 non-words) and provides grade norms from the second to the last grade of junior high school.

3. Writing-under-dictation of word, non-word and sentences-containing-homophones: ‘‘Batteria per la Valutazione della Dislessia e Disortografia volutiva’’ (“Battery for the assessment of developmental reading and spelling disorders”)3. This test assesses accuracy (expressed as the number of errors) in writing under dictation single unrelated words, non-words and sentences containing homophones, and provides grade norms from the second to the last grade of junior high school.

4. Forward/backward digit spans: “Test TEMA – Memoria e Apprendimento” (the Italian version of the “Test of Memory and Learning – TOMAL”)4. This tasks require immediate recall, respectively, forward and backward, of strings of numbers that are read aloud by the operator. The strings are increasingly longer at each step. Scores are computed based on the number of correct numbers recalled in the correct order for each string. Age norms are provided.

5. Phonemic elision and blending: “Prove metafonologiche” (“Phonemic awareness test”)5. These tasks require elision of a word’s first two phonemes and blending a span of phonemes read aloud by the operator, respectively. The number of accurate answers was recorded. Scores of both tasks were standardized (mean = 0, SD = 1) on norms provided from a sample of 96 healthy subjects5.

  1. Language abilities were assessed with the “Batteria per l’esame del linguaggio nel

bambino dai 4 ai 12 anni” (“Battery for the assessment of language abilities in children aged 4-12 years old”)6, a clinical tool widely used in Italy for the identification, diagnosis, and follow-up evaluation of languageimpairments in school-age children which provides language scores for each subscales for children from 4 to 12 years of age7. For the current purpose, only three receptive (auditory comprehension tapping syntax, vocabulary and semantic relationships) and two expressive tests were considered:

1)Semantic Comprehension (SC) assesses the child’s vocabulary size through a list of 32 words (nouns, adjectives, and verbs). Participants are asked to indicate as rapidly and accurately as possible which picture out of four (the target, two phonological and one semantic distractors) corresponds to the word orally presented by the examiner. A score of 1 is given to correct answers within 1 minute, otherwise the score is 0. The total score is the sum of obtained points at each command.

2)Token test (TOKEN) assesses verbal comprehension through a list of 21 commands of increasing syntactic complexity. 20 tokens of different shapes (i.e., circle and square), colors (red, blue, yellow, green and white) and sizes (two sizes) are presented. Participants are asked to execute as rapidly and accurately as possible a command orally given by the examiner. A score of 1 is assigned to correct performance within 5 seconds at first attempt and of 0.5 to correct performance within 5 seconds at second attempt; otherwise the score is 0. The total score is the sum of obtained points at each command.

3)Syntactic Comprehension (SYC) assesses verbal comprehension through a list of 76 sentences with increasing syntactic complexity. Participants are asked to indicate which picture out of four (the target and one grammatical, one lexical and one visual distractors) corresponds to the sentence orally presented by the examiner. Correct answers are scored 0; wrong answers are scored 0.5 at first and 1.5 at second attempt. The total score is the sum of obtained points at each command.

4)Rapid Automatized Naming (RAN) assesses phonological retrieval and processing speed. Participants are asked to name a visually presented stimuli as rapidly and accurately as possible. The stimuli adopted consisted of colors and objects. Colors are orange, yellow, pink and red. The objects are line drawings of 32 objects. A score of 1 is assigned to correct naming regardless of articulation errors within 10 seconds, otherwise the score is 0. The total score is the sum of obtained points at each command.

5)Semantic fluency (FLUENCY). Participants were asked to produce as many words as possible from two semantic categories (i.e., animals and objects) in a 1-minute interval each. The total score is the sum of words produced in the best trial.

Language scores were standardized (mean= 0, SD= 1) on norms provided from a sample of 160 subjects aged from 6 to 12 years of Italian ancestry and language, belonging to public and private school in Milan and Lecco7.

  1. Mathematics abilities were measured with “Test di valutazione delle Abilità di

Calcolo - AC-MT” (“Test for the assessment of mathematics abilities – AC-MT”)8 a standardized clinical tool widely used in Italy for the identification, diagnosis, and follow-up evaluation of mathematics impairments in school-age children which provides grade-normed scores for each subscales (mean= 0, SD= 1)9. For the current purposes, only the following tests were considered:

1)Mental calculation (MC) in which participants are asked to solve mentally and to give a verbal response as rapidly and accurately as possible to an orally presented list of two-digit addition, subtraction and multiplication increasing gradually in difficulty. A score of 0 is assigned to correct solutions within 30 seconds, otherwise the score is 1. Both speed (seconds; MC-Speed) and accuracy (number of errors; MC-Accuracy) are measured.

2)Written Calculation (WC) in which participants are asked to solve by writing as many as possible of a written presented list of two-digit addition, subtraction and multiplication increasing gradually in difficulty. A score of 0 is assigned to correct solutions, otherwise the score is 1. Both speed (seconds; WC-Speed) and accuracy (number of errors; WC-Accuracy) are measured.

3)Number Dictation (ND) in which participants write under dictation a list of numbers in the Arabic format increasing gradually in difficulty. This test gives information about syntactic and lexical mechanisms underlying number production. A score of 1 is assigned to correct solutions, otherwise the score is 0. The total score is the sum of obtained points at each command.

4)Numerical Facts (NF) taps the knowledge of addition and subtraction with one-digit numbers and multiplication tables; participants are asked to solve mentally and to give a verbal response as rapidly and accurately as possible to an orally presented list of addition, subtraction and multiplication with one-digit numbers increasing gradually in difficulty. A score of 0 is assigned to correct solutions within 5 seconds, otherwise the score is 1. The total score is the sum of obtained points at each command.

Grade norms from the second to the last grade of junior high school are provided.

Eighteen phenotypes were used in association analyses:

  1. DD as a discrete trait;
  2. READING-Accuracy, as measured by averaging accuracy, grade-standardized scores in single word and single non-word reading tasks3, since bivariate correlation was substantial (r= 0.640);
  3. READING-Speed, as measured by averaging speed, grade-standardized scores in single word and single non-word reading tasks3, since bivariate correlation was strong (r= 0.820);
  4. SPELLING, as measured by averaging the accuracy, grade-standardized scores in writing-under-dictation word, non-word and sentences-containing-homophones3 since mean bivariate correlations were substantial (r= 0.560);
  5. Auditory STM, as measured by averaging age-normed scores in the forward and backward digit spans4, inasmuch as bivariate correlation was substantial (r= 0.666);
  6. Phonemic elision5 (ELISION);
  7. Phonemic blending5 (BLENDING);
  8. Five language abilities, i.e., semantic comprehension (SC), Token test (TOKEN), syntactic comprehension (SYC), rapid automatized naming (RAN), and semantic fluency (FLUENCY);
  9. Six mathematics abilities, i.e., mental calculation (MC, both accuracy – MC-Accuracy, and speed - MC-Speed), written calculation (WC, both accuracy - WC-Accuracy, and speed - WC-Speed), number dictation (ND), and numerical facts (NF).

References:

  1. Cornoldi, C. & Colpo, G.Prove di lettura MT, nuove prove di lettura MT per la scuola media inferiore (Organizzazioni Speciali, 1995).
  2. Cornoldi, C. & Colpo, G. Prove di lettura MT per la scuola elementare – 2 (Organizzazioni Speciali, 1998).
  3. Sartori, G., Job, R. & Tressoldi, P.E.Batteria per la valutazione della dislessia e della disortografia evolutiva(Organizzazioni Speciali, 1995).
  4. Reynolds, C.R. & Bigler, E.D.Test of memory and learning(Erickson, 1994).
  5. Cossu, G., Shankweiler, D., Liberman, I.Y., Katz, L. & Tola, G. Awareness of phonological segments and reading ability in Italian children. Applied Psycholinguistics. 9: 1-16 (1988).
  6. Fabbro, F. Neurolinguistica e Neuropsicologia Dei Disturbi Specifici Del Linguaggio Nel Bambino: Proposta Di Un Esame Del Linguaggio. Saggi. Neuropsicologia Infantile, psicopedagogia, riabilitazione.1:11-23 (1999).
  7. Marino, C., Mascheretti, S., Riva, V., Cattaneo, F., Rigoletto, C., Rusconi, M. et al. Pleiotropic effects of DCDC2 and DYX1C1 genes on language and mathematics traits in nuclear families of developmental dyslexia.Behav. Genet. 41, 67-76 (2011).
  8. Cornoldi, C., Lucangeli, D. & Bellina, M.AC-MT, Test Di Valutazione Delle Abilità Di Calcolo - Gruppo MT(Erickson, 2003).
  9. Cornoldi, C. & Lucangeli, D. Arithmetic education and learning disabilities in Italy. J Learn Disabil.37: 42-49 (2004).