Human Genetics

, Volume 129, Issue 1, pp 59–70 | Cite as

Genome-scan for IQ discrepancy in autism: evidence for loci on chromosomes 10 and 16

  • Nicola H. Chapman
  • Annette Estes
  • Jeff Munson
  • Raphael Bernier
  • Sara J. Webb
  • Joseph H. Rothstein
  • Nancy J. Minshew
  • Geraldine Dawson
  • Gerard D. Schellenberg
  • Ellen M. WijsmanEmail author
Original Investigation


Performance IQ (PIQ) greater than verbal IQ (VIQ) is often observed in studies of the cognitive abilities of autistic individuals. This characteristic is correlated with social and communication impairments, key parts of the autism diagnosis. We present the first genetic analyses of IQ discrepancy (PIQ–VIQ) as an autism-related phenotype. We performed genome-wide joint linkage and segregation analyses on 287 multiplex families, using a Markov chain Monte Carlo approach. Genetic data included a genome-scan of 387 micro-satellite markers in 210 families augmented with additional markers added in a subset of families. Empirical P values were calculated for five interesting regions. Linkage analysis identified five chromosomal regions with substantial regional evidence of linkage; 10p12 [P = 0.001; genome-wide (gw) P = 0.05], 16q23 (P = 0.015; gw P = 0.53), 2p21 (P = 0.03, gw P = 0.78), 6q25 (P = 0.047, gw P = 0.91) and 15q23-25 (P = 0.053, gw P = 0.93). The location of the chromosome 10 linkage signal coincides with a region noted in a much earlier genome-scan for autism, and the chromosome 16 signal coincides exactly with a linkage signal for non-word repetition in specific language impairment. This study provides strong evidence for a QTL influencing IQ discrepancy in families with autistic individuals on chromosome 10, and suggestive evidence for a QTL on chromosome 16. The location of the chromosome 16 signal suggests a candidate gene, CDH13, a T-cadherin expressed in the brain, which has been implicated in previous SNP studies of autism and ADHD.


Autism Spectrum Disorder Markov Chain Monte Carlo Specific Language Impairment Autistic Individual Joint Segregation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Funding was provided by the Autism Centers of Excellence (HD055782). Some genotyping services were provided by the Center for Inherited Disease Research (CIDR), or supported by Autism Speaks, through collaboration with the Autism Genome Project. CIDR is funded through a federal contract from the NIH to The Johns Hopkins University, contract number HHSN268200782096C. We also gratefully acknowledge the contributions of the families who participated in this study, the contributions of the Clinical and Statistical Cores of the UW ACE for diagnostic and databasing support. The authors thank the anonymous reviewers for helpful comments that greatly improved this paper.

Conflict of interest

All authors report no conflicts of interest. Experiments conducted comply with the current laws of the country in which they were performed.

Supplementary material

439_2010_899_MOESM1_ESM.pdf (14 kb)
Online Resource 1: Plots of ADOS and ADI communication domain and social domain scores as a function of IQ discrepancy (PDF 14 kb)
439_2010_899_MOESM2_ESM.doc (36 kb)
Online Resource 2: Table of single-marker linkage results in regions of interest (DOC 36 kb)


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Nicola H. Chapman
    • 1
  • Annette Estes
    • 2
  • Jeff Munson
    • 2
  • Raphael Bernier
    • 2
  • Sara J. Webb
    • 2
  • Joseph H. Rothstein
    • 1
  • Nancy J. Minshew
    • 5
    • 6
  • Geraldine Dawson
    • 7
    • 8
  • Gerard D. Schellenberg
    • 9
  • Ellen M. Wijsman
    • 1
    • 3
    • 4
    • 10
    Email author
  1. 1.Department of MedicineUniversity of WashingtonSeattleUSA
  2. 2.Department of Psychiatry and Behavioral SciencesUniversity of WashingtonSeattleUSA
  3. 3.Department of BiostatisticsUniversity of WashingtonSeattleUSA
  4. 4.Department of Genome SciencesUniversity of WashingtonSeattleUSA
  5. 5.Department of PsychiatryUniversity of Pittsburgh School of MedicinePittsburghUSA
  6. 6.Department of NeurologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  7. 7.Autism SpeaksUniversity of North Carolina Chapel HillChapel HillUSA
  8. 8.Department of PsychiatryUniversity of North Carolina Chapel HillChapel HillUSA
  9. 9.Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  10. 10.SeattleUSA

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