Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people-Reference-Cited by-同舟云学术

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

Published:2022-08-23 Issue:35 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Eising Else¹^ORCID,Mirza-Schreiber Nazanin²,de Zeeuw Eveline L.³,Wang Carol A.⁴⁵,Truong Dongnhu T.⁶,Allegrini Andrea G.⁷,Shapland Chin Yang⁸⁹^ORCID,Zhu Gu¹⁰,Wigg Karen G.¹¹,Gerritse Margot L.¹,Molz Barbara¹^ORCID,Alagöz Gökberk¹^ORCID,Gialluisi Alessandro¹²¹³¹⁴^ORCID,Abbondanza Filippo¹⁵,Rimfeld Kaili⁷¹⁶^ORCID,van Donkelaar Marjolein¹,Liao Zhijie¹⁷^ORCID,Jansen Philip R.¹⁸¹⁹²⁰,Andlauer Till F. M.¹²²¹^ORCID,Bates Timothy C.²²^ORCID,Bernard Manon²³,Blokland Kirsten²⁴^ORCID,Bonte Milene²⁵,Børglum Anders D.²⁶²⁷²⁸,Bourgeron Thomas²⁹,Brandeis Daniel³⁰³¹³²³³,Ceroni Fabiola³⁴³⁵^ORCID,Csépe Valéria³⁶³⁷,Dale Philip S.³⁸^ORCID,de Jong Peter F.³⁹^ORCID,DeFries John C.⁴⁰⁴¹,Démonet Jean-François⁴²,Demontis Ditte²⁶²⁷^ORCID,Feng Yu¹¹,Gordon Scott D.¹⁰,Guger Sharon L.⁴³,Hayiou-Thomas Marianna E.⁴⁴^ORCID,Hernández-Cabrera Juan A.⁴⁵,Hottenga Jouke-Jan³,Hulme Charles⁴⁶^ORCID,Kere Juha⁴⁷⁴⁸,Kerr Elizabeth N.⁴³⁴⁹⁵⁰^ORCID,Koomar Tanner⁵¹,Landerl Karin⁵²⁵³,Leonard Gabriel T.⁵⁴,Lovett Maureen W.²⁴⁵⁰,Lyytinen Heikki⁵⁵,Martin Nicholas G.¹⁰,Martinelli Angela¹⁵,Maurer Urs⁵⁶,Michaelson Jacob J.⁵¹,Moll Kristina⁵⁷,Monaco Anthony P.⁵⁸^ORCID,Morgan Angela T.⁵⁹⁶⁰⁶¹^ORCID,Nöthen Markus M.⁶²^ORCID,Pausova Zdenka²³⁶³,Pennell Craig E.⁴⁵⁶⁴,Pennington Bruce F.⁶⁵^ORCID,Price Kaitlyn M.¹¹²⁴⁶⁶,Rajagopal Veera M.²⁶²⁷^ORCID,Ramus Franck⁶⁷,Richer Louis⁶⁸^ORCID,Simpson Nuala H.⁶⁹,Smith Shelley D.⁷⁰,Snowling Margaret J.⁶⁹⁷¹^ORCID,Stein John⁷²^ORCID,Strug Lisa J.⁷³⁷⁴^ORCID,Talcott Joel B.⁷⁵,Tiemeier Henning¹⁸⁷⁶,van der Schroeff Marc P.⁷⁷⁷⁸^ORCID,Verhoef Ellen¹^ORCID,Watkins Kate E.⁶⁹^ORCID,Wilkinson Margaret²⁴^ORCID,Wright Margaret J.⁷⁹,Barr Cathy L.¹¹²⁴⁶⁶^ORCID,Boomsma Dorret I.³⁸⁰⁸¹^ORCID,Carreiras Manuel⁸²⁸³⁸⁴^ORCID,Franken Marie-Christine J.⁷⁷,Gruen Jeffrey R.⁶^ORCID,Luciano Michelle²²^ORCID,Müller-Myhsok Bertram¹²⁸⁵^ORCID,Newbury Dianne F.³⁵,Olson Richard K.⁴⁰,Paracchini Silvia¹⁵,Paus Tomáš⁸⁶,Plomin Robert⁷,Reilly Sheena⁵⁹⁸⁷^ORCID,Schulte-Körne Gerd⁵⁷,Tomblin J. Bruce⁸⁸,van Bergen Elsje³⁸⁰⁸⁹,Whitehouse Andrew J. O.⁹⁰,Willcutt Erik G.⁴¹,St Pourcain Beate¹⁸⁹¹,Francks Clyde¹⁹¹⁹²^ORCID,Fisher Simon E.¹⁹¹^ORCID

Affiliation:

1. Language and Genetics Department, Max Planck Institute for Psycholinguistics, 6525 XD Nijmegen, the Netherlands

2. Institute of Neurogenomics, Helmholtz Zentrum Munich, 85764 Munich, Germany

3. Department of Biological Psychology, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, the Netherlands

4. School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW 2308, Australia

5. Mothers and Babies Research Program, Hunter Medical Research Institute, Newcastle, NSW 2305, Australia

6. Department of Pediatrics and Genetics, Yale Medical School, New Haven, CT 06510

7. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, United Kingdom

8. MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, United Kingdom

9. Population Health Sciences, University of Bristol, Bristol BS8 2PS, United Kingdom

10. Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia

11. Division of Experimental and Translational Neuroscience, Krembil Research Institute, University Health Network, Toronto, ON M5T 0S8, Canada

12. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany

13. Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, 86077 Pozzilli, Italy

14. Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy

15. School of Medicine, University of St Andrews, KY16 9TF, St. Andrews, Scotland

16. Department of Psychology, Royal Holloway, University of London, Egham TW20 0EY, United Kingdom

17. Department of Psychology, University of Toronto, Toronto, ON M5S 3G3,Canada

18. Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, 3000 CB Rotterdam, the Netherlands

19. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, 1081 HV the Netherlands

20. Department of Human Genetics, VU Medical Center, Amsterdam University Medical Center, 1081 BT Amsterdam, the Netherlands

21. Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany

22. Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, United Kingdom

23. Department of Physiology and Nutritional Sciences, University of Toronto, Toronto, ON M5S 1A1, Canada

24. Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, M5G 1X8 ON, Canada

25. Department of Cognitive Neuroscience and Maastricht Brain Imaging Center, Faculty of Psychology and Neuroscience, Maastricht University, 6229 ER Maastricht, the Netherlands

26. Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark

27. The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210 Aarhus, Denmark

28. Center for Genomics and Personalized Medicine (CGPM), 8000 Aarhus, Denmark

29. Human Genetics and Cognitive Functions, Institut Pasteur, UMR3571 Centre national de la recherche scientifique (CNRS), Université Paris Cité, Paris, 75015, France

30. Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, 8032 Zurich, Switzerland

31. Zurich Center for Integrative Human Physiology, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland

32. Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland

33. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany

34. Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy

35. Faculty of Health and Life Sciences, Oxford Brookes University, Oxford OX3 0BP, United Kingdom

36. Brain Imaging Centre, Research Centre for Natural Sciences, Budapest, 1117 Hungary

37. Multilingualism Doctoral School, Faculty of Modern Philology and Social Sciences, University of Pannonia, Veszprém, 8200 Hungary

38. Department of Speech & Hearing Sciences, University of New Mexico, Albuquerque, NM 87131

39. Department of Child Development and Education, University of Amsterdam, 1012 WX Amsterdam, the Netherlands

40. Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309-0447

41. Department of Psychology and Neuroscience, University of Colorado, Boulder, CO 80309-0447

42. Leenaards Memory Centre, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV), University of Lausanne, CH-1011 Lausanne, Switzerland

43. Department of Psychology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada

44. Department of Psychology, University of York, York YO10 5DD, United Kingdom

45. Departamento de Psicología, Clínica Psicobiología y Metodología, 38200, La Laguna, Santa Cruz de Tenerife, Spain

46. Department of Education, University of Oxford, Oxford, Oxfordshire OX2 6PY, United Kingdom

47. Department of Biosciences and Nutrition, Karolinska Institutet, 171 77 Stockholm, Sweden

48. Stem Cells and Metabolism Research Program, University of Helsinki and Folkhälsan Research Center, 00014 Helsinki, Finland

49. Department of Neurology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada

50. Department of Paediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada

51. Department of Psychiatry, University of Iowa, Iowa City, IA 52242

52. Institute of Psychology, University of Graz, 8010 Graz, Austria

53. BioTechMed-Graz, 8010 Graz, Austria

54. Cognitive Neuroscience Neurology and Neurosurgery, McGill University, Montreal, QC H3A 1G1, Canada

55. Department of Psychology, University of Jyväskylä, 40014 Jyväskylä, Finland

56. Department of Psychology, The Chinese University of Hong Kong, Hong Kong, China

57. Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwig-Maximilians-University Hospital Munich, Munich, 80336 Germany

58. Office of the President, Tufts University, Medford, MA 02155

59. Speech and Language, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia

60. Department of Audiology and Speech Pathology, University of Melbourne, Melbourne, VIC 3052, Australia

61. Speech Pathology Department, Royal Children's Hospital, Melbourne, VIC 3052, Australia

62. Institute of Human Genetics, University Hospital of Bonn, 53127 Bonn, Germany

63. Hospital for Sick Children, Toronto, ON M5G 1X8, Canada

64. Maternity and Gynaecology, John Hunter Hospital, Newcastle, NSW 2305, Australia

65. Department of Psychology, University of Denver, Denver, CO 80210

66. Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada

67. Laboratoire de Sciences Cognitives et Psycholinguistique, Ecole Normale Supérieure, Paris Sciences & Lettres University, École des Hautes Études en Sciences Sociales (EHESS), Centre National de la Recherche Scientifique (CNRS), Paris, 75005 France

68. Department of Health Sciences, Université du Québec à Chicoutimi, Chicoutimi, QC G7H 2B1, Canada

69. Department of Experimental Psychology, University of Oxford, Oxford OX2 6GG, United Kingdom

70. Department of Neurological Sciences, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198

71. St. John’s College, University of Oxford, Oxford OX1 3JP, United Kingdom

72. Department of Physiology, Anatomy and Genetics, Oxford University, Oxford OX1 3PT, United Kingdom

73. Department of Statistical Sciences and Computer Science and Division of Biostatistics, University of Toronto, Toronto, ON M5S 3G3, Canada

74. Program in Genetics and Genome Biology and the Centre for Applied Genomics, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada

75. Institute for Health and Neurodevelopment, Aston University, Birmingham B4 7ET, United Kingdom

76. T. H. Chan School of Public Health, Harvard, Boston, MA 02115

77. Department of Otolaryngology, Head and Neck Surgery, Erasmus University Medical Center, 3015 GD Rotterdam, the Netherlands

78. Generation R Study Group, Erasmus University Medical Center, 3015 GD Rotterdam, the Netherlands

79. Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia

80. Netherlands Twin Register, 1081 BT Amsterdam, the Netherlands

81. Amsterdam Reproduction and Development Research Institute, Amsterdam University Medical Center, 1105 AZ Amsterdam, the Netherlands

82. Basque Center on Cognition, Brain and Language, Donostia-San Sebastian, 20009 Gipuzkoa, Spain

83. Ikerbasque, Basque Foundation for Science, 48009 Bilbao, Vizcaya, Spain

84. Lengua Vasca y Comunicación, University of the Basque Country, 48940 Bilbao, Vizcaya, Spain

85. Department of Health Science, University of Liverpool, Liverpool L69 7ZX, United Kingdom

86. Department of Psychiatry and Neuroscience and Centre Hospitalier Universitaire Sainte Justine, University of Montreal, Montreal, QC H3T 1J4, Canada

87. Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD 4222, Australia

88. Communication Sciences and Disorders, University of Iowa, Iowa City, IA 52242

89. Research Institute LEARN!, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, the Netherlands

90. Telethon Kids Institute, The University of Western Australia, Perth, WA 6009, Australia

91. Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 EN Nijmegen, the Netherlands

92. Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands

Abstract

The use of spoken and written language is a fundamental human capacity. Individual 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 individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples 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.

Funder

Department of Health | National Health and Medical Research Council

Simons Foundation Autism Research Initiative

Koninklijke Nederlandse Akademie van Wetenschappen

HHS | National Institutes of Health

HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development

Agence Nationale de la Recherche

European Commission

ZonMw

Wellcome Trust

Royal Society

Lundbeckfonden