Skip to main content
SpringerLink
Log in

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

  • Published:
Behavior Genetics Aims and scope Submit manuscript

A genome-wide linkage scan of 795 microsatellite markers (761 autosomal, 34 X chromosome) was performed on Multidimensional Aptitude Battery subtests and verbal, performance and full scale scores, the WAIS-R Digit Symbol subtest, and two word-recognition tests (Schonell Graded Word Reading Test, Cambridge Contextual Reading Test) highly predictive of IQ. The sample included 361 families comprising 2–5 siblings who ranged in age from 15.7 to 22.2 years; genotype, but not phenotype, data were available for 81% of parents. A variance components analysis which controlled for age and sex effects showed significant linkage for the Cambridge reading test and performance IQ to the same region on chromosome 2, with respective LOD scores of 4.15 and 3.68. Suggestive linkage (LOD score>2.2) for various measures was further supported on chromosomes 6, 7, 11, 14, 21 and 22. Where location of linkage peaks converged for IQ subtests within the same scale, the overall scale score provided increased evidence for linkage to that region over any individual subtest. Association studies of candidate genes, particularly those involved in neural transmission and development, will be directed to genes located under the linkage peaks identified in this study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

Similar content being viewed by others

References

  • Abecasis, G. R. (2004). http://www.sph.umich.edu/csg/abecasis/Merlin/reference.html

  • Abecasis, G. R., Cherney, S. S., Cookson, W. O., and Cardon L. R. (2002). Merlin-rapid analysis of dense genetic maps using sparse gene flow trees. Nat. Genet. 30:97–101

    Article  PubMed  CAS  Google Scholar 

  • Addington, A. M., Gornick, M., Duckworth, J., Sporn, A., Gogtay, N., Bobb, A., Greenstein, D., Lenane, M., Gochman, P., Baker, N., Balkissoon, R., Vakkalanka, R. K., Weinberger, D. R., Rapoport, J. L., and Straub, R. E. (2004). GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD(67)), is associated with childhood-onset schizophrenia and cortical gray matter volume loss. Mol. Psychiatry. Advance online publication 26 October

  • Bacchelli, E., Blasi, F., Biondolillo, M., Lamb, J. A., Bonora, E., Barnby, G., Parr, J., Beyer, K. S., Klauck, S. M., Poustka, A., Bailey, A. J., Monaco, A. P., and Maestrini E. (2003). Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene. Mol. Psychiatry 8:916–924

    Article  PubMed  CAS  Google Scholar 

  • Beardsall, L., and Huppert, F. A. (1994). Improvement in NART word reading in demented and normal older persons using the Cambridge Contextual Reading Test. J. Clin. Exp. Neuropsychol. 16:232–242

    Article  PubMed  CAS  Google Scholar 

  • Cardon, L. R., Smith, S. D., Fulker, D. W., Kimberling, W.J., et al. (1994). Quantitative trait locus for reading disability of chromosome 6. Science 266:276–279

    Article  PubMed  CAS  Google Scholar 

  • Casto, S. D., DeFries, J. C., and Fulker, D. W. (1995) Multivariate genetic analysis of Wechsler Intelligence Scale for Children – Revised (WISC-R) factors. Behav. Genet. 25:25–32

    Article  PubMed  CAS  Google Scholar 

  • Carroll, J. B. (1993). Human Cognitive Abilities: A Survey of Factor-Analytic Studies. Cambridge: Cambridge University Press

    Google Scholar 

  • Cattell, R. B. (1963). Theory of fluid and crystallized intelligence: a critical experiment. J. Educ. Psychol. 54:1–22

    Article  Google Scholar 

  • Chorney, M. J., Chorney, K., Seese, N., Owen, M. J., Daniels, J., McGuffin, P., Thompson, L. A., Detterman, D. K., Benbow, C., Lubinski, D., Eley, T., and Plomin, R. (1998). A quantitative trait locus associated with cognitive ability in children. Psychol. Sci. 9:1–8

    Article  Google Scholar 

  • De Koning, D. J., Visscher, P. M., Knott, S. A., and Haley, C. S. (1998). A strategy for QTL detection in half-sib populations. Anim. Sci. 67:257–268

    Google Scholar 

  • Fagerheim, T., Raeymaekers, P., Tonnessen, F. E., Pedersen, M., Tranebjaerg, L., and Lubs, H. A. (1999) A new gene (DYX3) for dyslexia is located on chromosome 2. J. Med. Genet. 36:664–669

    PubMed  CAS  Google Scholar 

  • Fisher, S. E., Francks, C., Marlow, A. J., MacPhie, I. L., Newbury, D. F., Cardon, L. R., Ishikawa-Brush, Y., Richardson, A. J., Talcott, J. B., Gayan, J., Olson, R. K., Pennington, B. F., Smith, S. D., DeFries, J. C., Stein, J. F., and Monaco, A. P. (2002). Independent genome-wide scans identify a chromosome 18 quantitative-trait locus influencing dyslexia. Nat Genet. 30:86–91

    Article  PubMed  CAS  Google Scholar 

  • Gayan, J., Smith, S. D., Cherney, S. S., Cardon, L. R., Fulker, D. W., Brower, A. M., Olson, R. K., Pennington, B. F., and DeFries, J. C. (1999). Quantitative-trait locus for specific language and reading deficits on chromosome 6p. Am. J. Hum. Genet. 64:157–164

    Article  PubMed  CAS  Google Scholar 

  • Gustafsson, J.-E. (1984). A unifying model for the structure of intellectual abilities. Intelligence 8:179–203

    Article  Google Scholar 

  • Horn, J. L., and Cattell, R. B. (1966). Refinement and test of the theory of fluid and crystallized general intelligences. J. Educ. Psychol. 57:253–270

    Article  PubMed  CAS  Google Scholar 

  • Huntsman, M. M., Tran, B. V., Potkin, S. G., Bunney, W. E., Jr., and Jones, E. G. (1998). Altered ratios of alternatively spliced long and short gamma2 subunit mRNAs of the gamma-amino butyrate type A receptor in prefrontal cortex of schizophrenics. Proc. Natl. Acad. Sci. USA 95:15066–15071

    Article  PubMed  CAS  Google Scholar 

  • Jackson, D. N. (1984). Manual for the Multidimensional Aptitude Battery. Port Huron, MI: Research Psychologists Press

    Google Scholar 

  • Jackson, D. N. (1998). Multidimensional Aptitude Battery II. Port Huron, MI: Sigma Assessment Systems, Inc

    Google Scholar 

  • Kaminen, N., Hannula-Jouppi, K., Kestila, M., Lahermo, P., Muller, K., Kaaranen, M., Myllyluoma, B., Voutilainen, A., Lyytinen, H., Nopola-Hemmi, J., and Kere, J. (2003). A genome scan for developmental dyslexia confirms linkage to chromosome 2p11 and suggests a new locus on 7q32. J. Med. Genet. 40:340–345

    Article  PubMed  CAS  Google Scholar 

  • Kong, A., Gudbjartsson, D. F., Sainz, J., Jonsdottir, G. M., Gudjonsson, S. A., Richardsson, B., Sigurdardottir, S., Barnard, J., Hallbeck, B., Masson, G., Shlien, A., Palsson, S. T., Frigge, M. L., Thorgeirsson, T. E., Gulcher, J. R., and Stefansson, K. (2002). A high-resolution recombination map of the human genome. Nat. Genet. 31:241–247

    PubMed  CAS  Google Scholar 

  • Kruglyak, L., and Daly, M. J. (1998). Linkage thresholds for two-stage genome scans. Am. J. Hum. Genet. 62: 994–997

    Article  PubMed  CAS  Google Scholar 

  • Lander, E., and Kruglyak, L. (1995). Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat. Genet. 11:241–247

    Article  PubMed  CAS  Google Scholar 

  • Leal, S. M. (2003). Genetic maps of microsatellite and single-nucleotide polymorphism markers: are the distances accurate? Genet. Epidemiol. 24:243–252

    Article  PubMed  Google Scholar 

  • Legare, M. E., Bartlett, F. S., II, and Frankel, W. N. (2000). A major effect QTL determined by multiple genes in epileptic EL mice. Genome. Res. 10:42–48

    PubMed  CAS  Google Scholar 

  • Luciano, M., Hine, E. J., Wright, M. J., Duffy, D. L., and Martin, N. G. (in preparation). Combined linkage and association tests of SCA1, MJD and DPRLA triplet repeat polymorphisms with cognitive phenotypes in a normal population of adolescent twins

  • Luciano, M., Wright, M. J., Geffen, G. M., Geffen, L. B., Smith, G. A., Evans, D. M., and Martin, N. G. (2003). A genetic two-factor model of the covariation among a subset of Multidimensional Aptitude Battery and WAIS-R subtests. Intelligence 31:589–605

    Article  Google Scholar 

  • Luciano, M., Wright, M. J., Geffen, G. M., Geffen, L. B., Smith, G. A., and Martin, N. G. (2004a). A genetic investigation of the covariation among inspection time, choice reaction time, and IQ subtest scores. Behav. Genet. 34:41–50

    Article  Google Scholar 

  • Luciano, M., Wright, M. J., and Martin, N. G. (2004b). Exploring the etiology of the association between birthweight and IQ in an adolescent twin sample. Twin. Res. 7:62–71

    Article  PubMed  Google Scholar 

  • Martin, N. G., Boomsma, D. I., and Machin, G. A. (1997). A twin-pronged attack on complex traits. Nat. Genet. 17:87–392

    Article  Google Scholar 

  • Martin, N. G., and Eaves, L. J. (1977) The genetical analysis of covariance structure. Heredity 38:79–95

    Article  PubMed  CAS  Google Scholar 

  • McClearn, G. E., Johansson, B., Berg, S., Pederson, N. L., Ahern, F., Petrill, S. A., and Plomin, R. (1997) Substantial genetic influence on cognitive abilities in twins 80 or more years old. Science 276:1560–1563

    Article  PubMed  CAS  Google Scholar 

  • Nelson, H. E. (1982). National Adult Reading Test. Berkshire: NFER Nelson Publishing Company.

    Google Scholar 

  • Naeve, G. S., Ramakrishnan, M., Kramer, R., Hevroni, D., Citri, Y., and Theill, L. E. (1997) Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis. Proc. Natl. Acad. Sci. USA 94:2648–2653

    Article  PubMed  CAS  Google Scholar 

  • Pedersen, N. L., Plomin, R., and McClearn, G. E. (1994). Is there a G beyond g? (Is there genetic influence on specific cognitive abilities independent of genetic influence on general cognitive ability?). Intelligence 18:133–145

    Article  Google Scholar 

  • Petrill, S. A., Luo, D., Thompson, L. A., and Detterman, D. K. (1996a) The independent prediction of general intelligence by elementary cognitive tasks: genetic and environmental influences. Behav. Genet. 26:135–147

    Article  CAS  Google Scholar 

  • Petrill, S. A., Plomin, R., McClearn, G. E., Smith, D. L., Vignetti, S., Chorney, M. J., Chorney, K., Thompson, L. A., Detterman, D. K., Benbow, C., Lubinski, D., Daniels, J., Owen M. J., and McGuffin, P. (1996b) DNA markers associated with general and specific cognitive abilities. Intelligence 23:191–203

    Article  Google Scholar 

  • Petryshen, T. L., Kaplan, B. J., Hughes, M. L., Tzenova, J., and Field, L. L. (2002) Supportive evidence for the DYX3 dyslexia susceptibility gene in Canadian families. J. Med. Genet. 39:125–126

    Article  PubMed  CAS  Google Scholar 

  • Plomin, R. (1999) Genetics and general cognitive ability. Nature 402: C25–C29

    Article  PubMed  CAS  Google Scholar 

  • Plomin, R., Hill, L., Craig, I. W., McGuffin, P., Purcell, S., Sham, P. C., Thompson, L. A., Fisher, P. J., Turic, D., and Owen, M. J. (2001) A genome-wide scan of 1842 DNA markers for allelic associations with general cognitive ability: a five-stage design using DNA pooling and extreme selected groups. Behav. Genet. 31:497–509

    Article  PubMed  CAS  Google Scholar 

  • Plomin, R., McClearn, G. E., Smith, D. L., Skuder, P., Vignetti, S., Chorney, M. J., Chorney, K., Kasarda, S., Thompson, L. A., Detterman, D. K., Petrill, S. A., Daniels, J., Owen, M. J., and McGuffin, P. (1995) Allelic associations between 100 DNA markers and high versus low IQ. Intelligence 21:31–48

    Article  Google Scholar 

  • Plomin, R., McClearn, G. E., Smith, D. L., Vignetti, S., Chorney, M. J., Chorney, K., Venditti, C. P., Kasarda, S., Thompson, L. A., Detterman, D. K., Daniels, J., Owen, M., and McGuffin, P. (1994) DNA markers associated with high versus low IQ: the IQ quantitative trait loci (QTL) project. Behav. Genet. 24:107–118

    Article  PubMed  CAS  Google Scholar 

  • Plomin, R., Turic, D. M., Hill, L., Turic, D. E., Stephens, M., Williams, J., Owen, M. J., and O’Donovan, M. C. (2004) A functional polymorphism in the succinate-semialdehyde dehydrogenase (aldehyde dehydrogenase 5 family, member A1) gene is associated with cognitive ability. Mol. Psychiatry 9:582–586

    Article  PubMed  CAS  Google Scholar 

  • Posthuma, D., Luciano, M., Geus, E. J. d., Wright, M. J., Slagboom, E., Montgomery, G. W., Boomsma, D. I., and Martin N. G. (2005). A genome-wide scan for IQ in two independent samples identifies quantitative trait loci on 2q and 6p. Am J Hum Genet. 77:318–326

    Article  PubMed  CAS  Google Scholar 

  • Rabionet, R., Jaworski, J. M., Ashley-Koch, A. E., Martin, E. R., Sutcliffe, J. S., Haines, J. L., Delong, G. R., Abramson, R. K., Wright, H. H., Cuccaro, M. L., Gilbert, J. R., and Pericak-Vance, M. A. (2004) Analysis of the autism chromosome 2 linkage region: GAD1 and other candidate genes. Neurosci. Lett. 372: 209–214

    Article  PubMed  CAS  Google Scholar 

  • Rietveld, M. J. H., van Baal, C., Dolan, C. V., and Boomsma, D. I. (2000) Genetic factor analyses of specific cognitive abilities in 5-year-old Dutch children. Behav. Genet. 30: 29–40

    Article  PubMed  CAS  Google Scholar 

  • Rijsdijk, F. V., Vernon, P. A., and Boomsma, D. I. (1998) The genetic basis of the relation between speed-of-information-processing and IQ. Behav. Brain Res. 95:77–84

    Article  PubMed  CAS  Google Scholar 

  • Roberts, S. B., MacLean, C. J., Neale, M. C., Eaves, L. J., and Kendler, K. S. (1999) Replication of linkage studies of complex traits: an examination of variation in location estimates. Am. J. Hum. Genet. 65: 876–884

    Article  PubMed  CAS  Google Scholar 

  • Rujescu, D., Hartmann, A. M., Gonnermann, C., Moller, H. J., and Giegling, I. (2003) M129V variation in the prion protein may influence cognitive performance. Mol. Psychiatry 8:937–941

    Article  PubMed  CAS  Google Scholar 

  • Singer, S., Rossi, S., Verzosa, S., Hashim, A., Lonow, R., Cooper, T., Sershen, H., and Lajtha, A. (2004) Nicotine-induced changes in neurotransmitter levels in brain areas associated with cognitive function. Neurochem. Res. 29: 1779–1792

    Article  PubMed  CAS  Google Scholar 

  • Spelman, R. J., Coppieters, W., Karim, L., van Arendonk, J. A., and Bovenhuis, H. (1996) Quantitative trait loci analysis for five milk production traits on chromosome six in the Dutch Holstein-Friesian population. Genetics 144: 1799–1808

    PubMed  CAS  Google Scholar 

  • SPSS (1989–2003). SPSS 12.0.2 for Windows. SPSS Inc

  • Stober, G., Meyer, J., Nanda, I., Wienker, T. F., Saar, K., Knapp, M., Jatzke, S., Schmid, M., Lesch, K. P., and Beckmann, H. (2000) Linkage and family-based association study of schizophrenia and the synapsin III locus that maps to chromosome 22q13. Am. J. Med. Genet. 96: 392–397

    Article  PubMed  CAS  Google Scholar 

  • Toyooka, K., Muratake, T., Tanaka, T., Igarashi, S., Watanabe, H., Takeuchi, H., Hayashi, S., Maeda, M., Takahashi, M., Tsuji, S., Kumanishi, T., and Takahashi, Y. (1999) 14–3-3 protein eta chain gene (YWHAH) polymorphism and its genetic association with schizophrenia. Am. J. Med. Genet. 88: 164–167

    Article  PubMed  CAS  Google Scholar 

  • Tsai, S. J., Hong, C. J., Yu, Y. W., and Chen, T. J. (2004) Association study of a brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and personality trait and intelligence in healthy young females. Neuropsychobiology 49:13–16

    Article  PubMed  CAS  Google Scholar 

  • van Wezel, T., Ruivenkamp, C. A., Stassen, A. P., Moen, C. J., and Demant, P. (1999) Four new colon cancer susceptibility loci, Scc6 to Scc9 in the mouse. Cancer Res. 59:4216–4218

    PubMed  Google Scholar 

  • Vink, J. M., and Boomsma, D. I. (2002) Gene finding strategies. Biol. Psychol. 61:53–71

    Article  PubMed  Google Scholar 

  • Wainwright, M. A., Wright, M. J., Geffen, G. M., Geffen, L. B., Luciano, M., Martin, N. G. (2004) Genetic and environmental sources of covariance between reading tests used in neuropsychological assessment and IQ subtests. Behav. Genet. 34:365–376

    Article  PubMed  Google Scholar 

  • Wainwright, M. A., Wright, M. J., Geffen, G. M., Luciano, M., and Martin, N. G. (2005) The genetic basis of academic achievement on the Queensland Core Skills Test and its shared genetic variance with IQ. Behav. Genet. 35:133–145

    Article  PubMed  Google Scholar 

  • Ward, L. C., Ryan, J. J., and Axelrod, B. N. (2000) Confirmatory factor analyses of the WAIS-III standardization data. Psychol. Assess. 12:341–345

    Article  PubMed  CAS  Google Scholar 

  • Wiltshire, S., Cardon, L. R., and McCarthy, M. I. (2002) Evaluating the results of genomewide linkage scans of complex traits by locus counting. Am. J. Hum. Genet. 71:1175–1182

    Article  PubMed  CAS  Google Scholar 

  • Wright, M. J., De Geus, E., Ando, J., Luciano, M., Posthuma, D., Ono, Y., Hansell, N. K., Van Baal, C., Hiraishi, K., Hasegawa, T., Smith, G., Geffen, G., Geffen, L., Kanba, S., Miyake, A., Martin, N., and Boomsma, D. (2001) Genetics of cognition: outline of collaborative twin study. Twin Res. 4:48–56

    Article  PubMed  CAS  Google Scholar 

  • Yalcin, B., Willis-Owen, S. A., Fullerton, J., Meesaq, A., Deacon, R. M., Rawlins, J. N., Copley, R. R., Morris, A. P., Flint, J., and Mott, R. (2004) Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice. Nat. Genet. 36:1197–1202

    Article  PubMed  CAS  Google Scholar 

  • Zeng, Z., Fan, P., Rand, E., Kyaw, H., Su, K., Madike, V., Carter, K. C., and Li, Y. (1998) Cloning of a putative human neurotransmitter receptor expressed in skeletal muscle and brain. Biochem. Biophys. Res. Commun. 242:575–578

    Article  PubMed  CAS  Google Scholar 

  • Zhu, G., Duffy, D. L., Eldridge, A., Grace, M., Mayne, C., O’Gorman, L., Aitken, J. F., Neale, M., Hayward, N. K., Green, A. C., and Martin, N. G. (1999) A major quantitative-trait locus for mole density is linked to the familial melanoma gene CDKN2A: a maximum-likelihood combined linkage and association analysis in twins and their sibs. Am. J. Hum. Genet. 65:483–492

    Article  PubMed  CAS  Google Scholar 

  • Zhu, G., Evans, D. M., Duffy, D. L., Montgomery, G. W., Medland, S. E., Gillespie, N. A., Ewen, K. R., Jewell, M., Liew, Y. W., Hayward, N. K., Sturm, R. A., Trent, J. M., and Martin, N. G. (2004) A genome scan for eye color in 502 twin families: most variation is due to a QTL on chromosome 15q. Twin Res. 7:197–210

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We should like to thank the twins and their parents for their co-operation, Manuel Ferreira and Sarah Medland for assistance with data simulations and linkage analysis, Anjali Henders for blood processing and Megan Campbell for DNA extraction. Phenotype collection was funded by ARC grants (A79600334, A79906588, A79801419, DP0212016, DP0343921) and genotyping by the Australian NHMRC’s Program in Medical Genomics (NHMRC–219178) and the Center for Inherited Disease Research (CIDR; Director, Dr Jerry Roberts) at The Johns Hopkins University. CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (Contract Number N01-HG-65403). Dr Luciano is supported by an Australian Research Council Postdoctoral Fellowship (DP0449598).

Author information

Authors and Affiliations

  1. Queensland Institute of Medical Research, Herston, Brisbane, Australia

    M. Luciano, M. J. Wright, D. L. Duffy, M. A. Wainwright, G. Zhu, D. M. Evans, G. M. Geffen, G. W. Montgomery & N. G. Martin

Authors
  1. M. Luciano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. J. Wright
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. L. Duffy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. A. Wainwright
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. M. Evans
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. M. Geffen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G. W. Montgomery
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. N. G. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Luciano.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luciano, M., Wright, M., Duffy, D. et al. Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q. Behav Genet 36, 45–55 (2006). https://doi.org/10.1007/s10519-005-9003-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10519-005-9003-1

Keywords

Search

Navigation