GWAS for executive function and processing speed suggests involvement of the CADM2 gene

C A Ibrahim-Verbaas^{1

2

3}, J Bressler^{4

3}, S Debette^{5

6

7

3}, M Schuur^{1

2

3}, A V Smith^{8

9

3}, J C Bis^{10

3}, G Davies^{11

3}, S Trompet^{12

13}, J A Smith¹⁴, C Wolf¹⁵, L B Chibnik¹⁶, Y Liu¹⁷, V Vitart¹⁸, M Kirin¹⁹, K Petrovic²⁰, O Polasek²¹, L Zgaga²², C Fawns-Ritchie¹¹, P Hoffmann^{23

24

25}, J Karjalainen²⁶, J Lahti^{27

28}, D J Llewellyn²⁹, C O Schmidt³⁰, K A Mather³¹, V Chouraki³², Q Sun³³, S M Resnick³⁴, L M Rose³⁵, C Oldmeadow³⁶, M Stewart¹⁹, B H Smith³⁷, V Gudnason^{8

9}, Q Yang^{38

39}, S S Mirza^{40

41}, J W Jukema¹², P L deJager¹⁶, T B Harris⁴², D C Liewald^{11

43}, N Amin¹, L H Coker⁴⁴, O Stegle⁴⁵, O L Lopez⁴⁶, R Schmidt²⁰, A Teumer⁴⁷, I Ford⁴⁸, N Karbalai¹⁵, J T Becker^{46

49

50}, M K Jonsdottir⁵¹, R Au^{5

38}, Rsn Fehrmann²⁶, S Herms^{24

25}, M Nalls⁵², W Zhao¹⁴, S T Turner⁵³, K Yaffe⁵⁴, K Lohman¹⁷, J C van Swieten², Slr Kardia¹⁴, D S Knopman⁵⁵, W M Meeks⁵⁶, G Heiss⁵⁷, E G Holliday³⁶, P W Schofield⁵⁸, T Tanaka⁵⁹, D J Stott⁶⁰, J Wang³⁹, P Ridker³⁵, A J Gow^{11

43}, A Pattie¹¹, J M Starr^{11

61}, L J Hocking⁶², N J Armstrong^{31

63

64}, S McLachlan¹⁹, J M Shulman^{65

66}, L C Pilling⁶⁷, G Eiriksdottir⁸, R J Scott³⁶, N A Kochan^{31

68}, A Palotie^{69

70

71}, Y-C Hsieh⁷², J G Eriksson^{28

73

74

75

76}, A Penman⁷⁷, R F Gottesman⁷⁸, B A Oostra¹, L Yu⁷⁹, A L DeStefano^{5

38

39}, A Beiser^{5

38

39}, M Garcia⁴², J I Rotter^{80

81

82}, M M Nöthen^{25

83}, A Hofman^{40

41}, P E Slagboom⁸⁴, Rgj Westendorp⁸⁵, B M Buckley⁸⁶, P A Wolf^{5

38}, A G Uitterlinden^{40

41

87}, B M Psaty^{10

88

89

90}, H J Grabe⁹¹, S Bandinelli³, D I Chasman³⁵, F Grodstein³³, K Räikkönen²⁷, J-C Lambert³², D J Porteous⁹²; Generation Scotland; J F Price¹⁹, P S Sachdev^{31

68}, L Ferrucci⁵⁹, J R Attia³⁶, I Rudan¹⁹, C Hayward¹⁸, A F Wright¹⁸, J F Wilson¹⁹, S Cichon^{24

25

93}, L Franke²⁶, H Schmidt²⁰, J Ding⁹⁴, Ajm de Craen¹³, M Fornage⁹⁵, D A Bennett^#⁷⁹, I J Deary^#^{11

43}, M A Ikram^#^{2

40

41

96}, L J Launer^#⁴², A L Fitzpatrick^#⁸⁸, S Seshadri^#^{5

38}, C M van Duijn^#^{1

41}, T H Mosley^#⁹⁷

Affiliations

¹ Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
² Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.
³ Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
⁴ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁵ Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
⁶ Institut National de la Santé et de la Recherche Médicale (INSERM), U897, Epidemiology and Biostatistics, University of Bordeaux, Bordeaux, France.
⁷ Department of Neurology, Bordeaux University Hospital, Bordeaux, France.
⁸ Icelandic Heart Association, Kopavogur, Iceland.
⁹ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
¹⁰ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
¹¹ Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK.
¹² Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
¹³ Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
¹⁴ Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
¹⁵ RG Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany.
¹⁶ Program in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
¹⁷ Department of Epidemiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
¹⁸ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
¹⁹ Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
²⁰ Department of Neurology, Medical University and General Hospital of Graz, Graz, Austria.
²¹ Department of Public Health, University of Split, Split, Croatia.
²² Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland.
²³ Institute of Neuroscience and Medicine (INM -1), Research Center Juelich, Juelich, Germany.
²⁴ Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland.
²⁵ Department of Genomics, Life and Brain Research Center, Institute of Human Genetics, University of Bonn, Bonn, Germany.
²⁶ Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
²⁷ Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
²⁸ Folkhälsan Research Centre, Helsinki, Finland.
²⁹ Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, UK.
³⁰ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
³¹ Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Australia.
³² Inserm, U1167, Institut Pasteur de Lille, Université Lille-Nord de France, Lille, France.
³³ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
³⁴ Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Baltimore, MD, USA.
³⁵ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
³⁶ Hunter Medical Research Institute and Faculty of Health, University of Newcastle, Newcastle, NSW, Australia.
³⁷ Medical Research Institute, University of Dundee, Dundee, UK.
³⁸ The National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
³⁹ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁴⁰ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁴¹ Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands.
⁴² Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
⁴³ Department of Psychology, University of Edinburgh, Edinburgh, UK.
⁴⁴ Division of Public Health Sciences and Neurology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
⁴⁵ Max Planck Institute for Developmental Biology, Max Planck Institute for Intelligent Systems, Tübingen, Germany.
⁴⁶ Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
⁴⁷ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
⁴⁸ Robertson Center for biostatistics, University of Glasgow, Glasgow, UK.
⁴⁹ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
⁵⁰ Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
⁵¹ Landspitali Hospital, Reykjavik, Iceland.
⁵² Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
⁵³ Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
⁵⁴ Departments of Psychiatry, Neurology and Epidemiology, University of California, San Francisco and San Francisco VA Medical Center, San Francisco, CA, USA.
⁵⁵ Department of Neurology, Mayo Clinic, Rochester, MN, USA.
⁵⁶ Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA.
⁵⁷ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵⁸ School of Medicine and Public Health, Faculty of Health, University of Newcastle, Newcastle, SW, Australia.
⁵⁹ Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
⁶⁰ Department of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
⁶¹ Alzheimer Scotland Research Centre, Edinburgh, UK.
⁶² Division of Applied Medicine, University of Aberdeen, Aberdeen, UK.
⁶³ Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
⁶⁴ School of Mathematics & Statistics and Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.
⁶⁵ Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
⁶⁶ Department of Molecular and Human Genetics, The Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
⁶⁷ Epidemiology and Public Health Group, University of Exeter Medical School, Exeter, UK.
⁶⁸ Neuropsychiatric Institute, The Prince of Wales Hospital, Sydney, NSW, Australia.
⁶⁹ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
⁷⁰ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
⁷¹ Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
⁷² School of Public Health, Taipei Medical University, Taipei, Taiwan.
⁷³ Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
⁷⁴ National Institute for Health and Welfare, Helsinki, Finland.
⁷⁵ Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland.
⁷⁶ Vasa Central Hospital, Vasa, Finland.
⁷⁷ Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS, USA.
⁷⁸ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷⁹ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
⁸⁰ Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁸¹ Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
⁸² Division of Genetic Outcomes, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.
⁸³ German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
⁸⁴ Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
⁸⁵ Leiden Academy of Vitality and Ageing, Leiden, The Netherlands.
⁸⁶ Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.
⁸⁷ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁸⁸ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁸⁹ Department of Health Services, University of Washington, Seattle, WA, USA.
⁹⁰ Group Health Research Institute, Group Health, Seattle, WA, USA.
⁹¹ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS-Hospital Stralsund, Stralsund, Germany.
⁹² Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
⁹³ Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany.
⁹⁴ Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁹⁵ Institute for Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁹⁶ Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁹⁷ Department of Medicine and Neurology, University of Mississippi Medical Center, Jackson, MS, USA.

^# Contributed equally.

PMID: 25869804
PMCID: PMC4722802
DOI: 10.1038/mp.2015.37

Comparative Study

GWAS for executive function and processing speed suggests involvement of the CADM2 gene

C A Ibrahim-Verbaas et al. Mol Psychiatry. 2016 Feb.

. 2016 Feb;21(2):189-197.

doi: 10.1038/mp.2015.37. Epub 2015 Apr 14.

Authors

Affiliations

¹ Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
² Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.
³ Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
⁴ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁵ Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
⁶ Institut National de la Santé et de la Recherche Médicale (INSERM), U897, Epidemiology and Biostatistics, University of Bordeaux, Bordeaux, France.
⁷ Department of Neurology, Bordeaux University Hospital, Bordeaux, France.
⁸ Icelandic Heart Association, Kopavogur, Iceland.
⁹ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
¹⁰ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
¹¹ Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK.
¹² Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
¹³ Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
¹⁴ Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
¹⁵ RG Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany.
¹⁶ Program in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
¹⁷ Department of Epidemiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
¹⁸ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
¹⁹ Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
²⁰ Department of Neurology, Medical University and General Hospital of Graz, Graz, Austria.
²¹ Department of Public Health, University of Split, Split, Croatia.
²² Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland.
²³ Institute of Neuroscience and Medicine (INM -1), Research Center Juelich, Juelich, Germany.
²⁴ Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland.
²⁵ Department of Genomics, Life and Brain Research Center, Institute of Human Genetics, University of Bonn, Bonn, Germany.
²⁶ Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
²⁷ Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
²⁸ Folkhälsan Research Centre, Helsinki, Finland.
²⁹ Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, UK.
³⁰ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
³¹ Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Australia.
³² Inserm, U1167, Institut Pasteur de Lille, Université Lille-Nord de France, Lille, France.
³³ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
³⁴ Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Baltimore, MD, USA.
³⁵ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
³⁶ Hunter Medical Research Institute and Faculty of Health, University of Newcastle, Newcastle, NSW, Australia.
³⁷ Medical Research Institute, University of Dundee, Dundee, UK.
³⁸ The National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
³⁹ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁴⁰ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁴¹ Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands.
⁴² Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
⁴³ Department of Psychology, University of Edinburgh, Edinburgh, UK.
⁴⁴ Division of Public Health Sciences and Neurology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
⁴⁵ Max Planck Institute for Developmental Biology, Max Planck Institute for Intelligent Systems, Tübingen, Germany.
⁴⁶ Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
⁴⁷ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
⁴⁸ Robertson Center for biostatistics, University of Glasgow, Glasgow, UK.
⁴⁹ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
⁵⁰ Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
⁵¹ Landspitali Hospital, Reykjavik, Iceland.
⁵² Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
⁵³ Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
⁵⁴ Departments of Psychiatry, Neurology and Epidemiology, University of California, San Francisco and San Francisco VA Medical Center, San Francisco, CA, USA.
⁵⁵ Department of Neurology, Mayo Clinic, Rochester, MN, USA.
⁵⁶ Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA.
⁵⁷ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵⁸ School of Medicine and Public Health, Faculty of Health, University of Newcastle, Newcastle, SW, Australia.
⁵⁹ Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
⁶⁰ Department of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
⁶¹ Alzheimer Scotland Research Centre, Edinburgh, UK.
⁶² Division of Applied Medicine, University of Aberdeen, Aberdeen, UK.
⁶³ Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
⁶⁴ School of Mathematics & Statistics and Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.
⁶⁵ Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
⁶⁶ Department of Molecular and Human Genetics, The Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
⁶⁷ Epidemiology and Public Health Group, University of Exeter Medical School, Exeter, UK.
⁶⁸ Neuropsychiatric Institute, The Prince of Wales Hospital, Sydney, NSW, Australia.
⁶⁹ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
⁷⁰ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
⁷¹ Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
⁷² School of Public Health, Taipei Medical University, Taipei, Taiwan.
⁷³ Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
⁷⁴ National Institute for Health and Welfare, Helsinki, Finland.
⁷⁵ Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland.
⁷⁶ Vasa Central Hospital, Vasa, Finland.
⁷⁷ Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS, USA.
⁷⁸ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷⁹ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
⁸⁰ Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁸¹ Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
⁸² Division of Genetic Outcomes, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.
⁸³ German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
⁸⁴ Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
⁸⁵ Leiden Academy of Vitality and Ageing, Leiden, The Netherlands.
⁸⁶ Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.
⁸⁷ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁸⁸ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁸⁹ Department of Health Services, University of Washington, Seattle, WA, USA.
⁹⁰ Group Health Research Institute, Group Health, Seattle, WA, USA.
⁹¹ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS-Hospital Stralsund, Stralsund, Germany.
⁹² Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
⁹³ Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany.
⁹⁴ Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁹⁵ Institute for Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁹⁶ Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁹⁷ Department of Medicine and Neurology, University of Mississippi Medical Center, Jackson, MS, USA.

^# Contributed equally.

PMID: 25869804
PMCID: PMC4722802
DOI: 10.1038/mp.2015.37

Abstract

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

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Figures

**Figure 1**
Gene network plot for *CADM2*, based on biological processes. Gray lines indicate positive co-expression and blue lines indicate negative co-expression, with the density of the line reflecting the strength of the co-expression.

See this image and copyright information in PMC

References

1. Green MF. Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry. 2006;67:3–8. discussion 36-42. - PubMed
1. Seidman LJ, Biederman J, Weber W, Hatch M, Faraone SV. Neuropsychological function in adults with attention-deficit hyperactivity disorder. Biol Psychiatry. 1998;44:260–268. - PubMed
1. Huntley JD, Howard RJ. Working memory in early Alzheimer's disease: a neuropsychological review. Int J Geriatr Psychiatry. 2009;25:121–132. - PubMed
1. Salthouse TA. The processing-speed theory of adult age differences in cognition. Psychol Rev. 1996;103:403–428. - PubMed
1. Luciano M, Hansell NK, Lahti J, Davies G, Medland SE, Raikkonen K, et al. Whole genome association scan for genetic polymorphisms influencing information processing speed. Biol Psychol. 2011;86:193–202. - PMC - PubMed

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GWAS for executive function and processing speed suggests involvement of the CADM2 gene

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GWAS for executive function and processing speed suggests involvement of the CADM2 gene

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