dc.description.abstract | Reading Disability (RD) is often characterized by difficulties in the phonology of the language. While the molecular mechanisms
underlying it are largely undetermined, loci are being revealed by genome-wide association studies (GWAS). In a previous GWAS for
word reading (Price, 2020), we observed that top single-nucleotide polymorphisms (SNPs) were located near to or in genes involved
in neuronal migration/axon guidance (NM/AG) or loci implicated in autism spectrum disorder (ASD). A prominent theory of RD
etiology posits that it involves disturbed neuronal migration, while potential links between RD-ASD have not been extensively
investigated. To improve power to identify associated loci, we up-weighted variants involved in NM/AG or ASD, separately, and
performed a new Hypothesis-Driven (HD)–GWAS. The approach was applied to a Toronto RD sample and a meta-analysis of the
GenLang Consortium. For the Toronto sample (n = 624), no SNPs reached significance; however, by gene-set analysis, the joint
contribution of ASD-related genes passed the threshold (p~1.45 × 10–2, threshold = 2.5 × 10–2). For the GenLang Cohort
(n = 26,558), SNPs in DOCK7 and CDH4 showed significant association for the NM/AG hypothesis (sFDR q = 1.02 × 10–2). To make
the GenLang dataset more similar to Toronto, we repeated the analysis restricting to samples selected for reading/language deficits
(n = 4152). In this GenLang selected subset, we found significant association for a locus intergenic between BTG3-C21orf91 for both
hypotheses (sFDR q < 9.00 × 10–4). This study contributes candidate loci to the genetics of word reading. Data also suggest that,
although different variants may be involved, alleles implicated in ASD risk may be found in the same genes as those implicated in
word reading. This finding is limited to the Toronto sample suggesting that ascertainment influences genetic associations. | es_ES |
dc.description.sponsorship | We thank the psychometrists and volunteers that assisted with this project over the
years and the participants in this study. We would like to thank also Dr. Lei Sun for
her statistical guidance using SFDR. Support for the Toronto project was provided by
grants from the Canadian Institutes of Health Research (MOP-133440 and PJT-
180419). K.P. was supported by the Hospital for Sick Children Research Training
Program. E.E. and S.E.F. are supported by the Max Planck Society. GenLang
Consortium Acknowledgements. As stated by Eising et al. (2022): B.M., B.M.-M.,
B.S.P., C.F., E.E., E.V., G.A., M.v.D., and S.E.F. are supported by the Max Planck Society.
A.G. and T.F.M.A. were supported by the Munich Cluster for Systems Neurology
(SyNergy), and A.G. was supported by Fondazione Umberto Veronesi. A.T.M. is
supported by National Health and Medical Research Council of Australia (NHMRC)
Grants 1105008 and 1195955 and Centre of Research Excellence Grant 1116976.
A.J.O.W. is supported by NHMRC Grant 1173896. B.S.P. is supported by Simons Foundation Autism Research Initiative Grant 514787. C.Y.S. works in the Medical
Research Council Integrative Epidemiology Unit at the University of Bristol
(MC_UU_00011/3). D.I.B. acknowledges Royal Netherlands Academy of Science
Professor Award PAH/6635. E.E. is supported by NIH Grant R01DC016977. E.G.W. and
J.R.G. are supported by National Institute of Child Health and Human Development
(NICHD) Grant P50 HD 27802. F.R. is supported by Agence Nationale de la Recherche
Grants ANR-06-NEURO-019-01, ANR-17-EURE-0017 IEC, ANR-10-IDEX-0001-02 PSL,
and ANR-11-BSV4-014-01 and European Commission Grant LSHM-CT-2005-018696.
H.T. is supported by the Netherlands Organization for Scientific Research (NWO) and
Netherlands Organisation for Health Research and Development (ZonMW) Grant VICI
016.VICI.170.200. J.C.D. was supported by NICHD Grant P50 HD 27802. J.J.M., J.B.To.,
and T.K. were supported by NIH Grant R01 DC014489. K.M.P. was supported by the
Hospital for Sick Children Research Training Program (Restracomp). K.R. is supported
by a Sir Henry Wellcome Postdoctoral Fellowship (213514/Z/18/Z). M.J.S. is supported
by Wellcome Trust Grant WT082032MA. S.P. and F.A. are supported by Royal Society
Grants UF150663 and RGF\EA\180141. T.B. is supported by Institut Pasteur, the
Bettencourt-Schueller Foundation, and Université de Paris. The Adolescent Brain
Cognitive Development Study is supported by the NIH and additional federal
partners (NIH Grants U01DA041048, U01DA050989, U01DA051016, U01DA041022,
U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106,
U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039,
U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148,
U01DA041093, U01DA041089, U24DA041123, and U24DA041147). The Aston Cohort
was supported by funding from European Union (EU) Horizon 2020 Programme
641652 and Waterloo Foundation Grant 797/17290. The St. Andrews Bioinformatics
Unit is funded by Wellcome Trust Grants 105621/Z/14/Z and 204821/Z/16/Z. ALSPAC
is supported by UK Medical Research Council and Wellcome Grant 217065/Z/19/Z
and the University of Bristol. A comprehensive list of grant funding is available on the
ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grantacknowledgements.
pdf). The Basque Center on Cognition, Brain and Language
(BCBL) cohort was supported by the Basque Government through the Basic
Excellence Research Centre program and the Agencia Estatal de Investigación
through BCBL Severo Ochoa excellence accreditation. The Brisbane Adolescent Twin
Sample was supported by Australian Research Council Grants A7960034, A79906588,
A79801419, DP0212016, and DP0343921, with genotyping funded by the NHMRC
Grant 389891. The Colorado Learning Disabilities Research Center cohort was
supported by NICHD Grant P50 HD 27802. The Early Language in Victoria Study was
supported by NHMRC Grant 436958. The Familial Influences on Literacy Abilities
cohort is supported by the University of Amsterdam, the Max Planck Institue
Nijmegen, and NWO Grants Rubicon 446-12-005 and VENI 451-15-017. The Iowa
study was funded by DC00496 and DC02746 from the National Institute on Deafness
and Other Communication Disorders (NIDCD). The GRaD study was funded by the
Manton Foundation, NIH Grants P50-HD027802 and K99-HD094902, and the Lambert
Family. NeuroDys was funded by an EU Sixth Framework Program grant to the
NeuroDys Consortium, Swiss National Science Foundation Grant 32-108130, and
Austrian Science Fund Grant 18351-B02. The Netherlands Twin Register is funded by
NWO Grants 480-04-004, 481-08-011, 056-32-010, 024.001.003, 480-15-001/674,
184.021.007, 184.033.111, and 56-464-14192; ZonMW Grants 911-09-032 and 912-
10-020; the Amsterdam Public Health and Amsterdam Reproduction and Development
Research Institutes; European Science Council Grant ERC Advanced 230374; EU
Seventh Framework Program (FP7) Grant FP7/2007-2013: 602768; National Institute
of Mental Health (NIMH) Grants U24 MH068457-06, R01 MH58799-03, and 1RC2
MH089995; and the Avera Institute for Human Genetics. The Pediatric Imaging,
Neurocognition, and Genetics cohort is funded by NIH Grant RC2DA029475, the
National Institute on Drug Abuse, and the Eunice Kennedy Shriver NICHD. The
Philadelphia Neurodevelopmental Cohort is funded by NIH Grants RC2MH089983
and RC2MH089924, an institutional development award to the Center for Applied
Genomics from The Children’s Hospital of Philadelphia, and a donation from Adele
and Daniel Kubert and thanks the NIH data repository. The Raine study was
supported by long-term funding from NHMRC Grants 572613, 403981, 1059711,
634445, 634509, and 1021105 and Canadian Institutes of Health Research (CIHR)
Grant MOP-82893. Funding was also provided by the University of Western Australia,
Curtin University, the Women and Infants Research Foundation, the Telethon Kids
Institute, Edith Cowan University, Murdoch University, the University of Notre Dame
Australia, and the Raine Medical Research Foundation. The Raine study analyses were
supported by the Pawsey Supercomputing Centre with funding from the Australian
Government and the Government of Western Australia. The Saguenay Youth Study is
supported by the CIHR, the Heart and Stroke Foundation of Quebec, and the
Canadian Foundation for Innovation. The SLI Consortium was funded by Wellcome
Trust Grant 076566 and UK Medical Research Council Grant G1000569. The Twins
Early Development Study is supported by UK Medical Research Council Grants MR/
V012878/1 and MR/M021475/1, NIH Grant AG046938, and the EU FP7 grant FP7/
2007-2013/: 602768. Toronto was supported by CIHR Grant MOP-133440. UK Dyslexia
was supported by Wellcome Trust Grants 076566/Z/05/Z and 075491/Z/04, Waterloo
Foundation Grant 797–1720, EU Grant 018696, and Royal Society Grant UF100463.
The York cohort was funded by Wellcome Trust Grant 082036/B/07/Z. | es_ES |