The Journal of Pediatrics
Volume 155, Issue 6 , Pages 909-913, December 2009

A Genome-Wide Association Study Identifies a Locus for Nonsyndromic Cleft Lip with or without Cleft Palate on 8q24

  • Struan F.A. Grant, PhD

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
    • Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA
    • Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA
    • Corresponding Author InformationReprint requests: Struan Grant, PhD, Center for Applied Genomics, 1216 E. Abramson Research Center, 3615 Civic Center Blvd, Philadelphia, PA 19104-4318.
  • ,
  • Kai Wang, PhD

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Haitao Zhang, PhD

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Wendy Glaberson, BA

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Kiran Annaiah, MSc

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Cecilia E. Kim, BA

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Jonathan P. Bradfield, BS

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Joseph T. Glessner, MSc

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Kelly A. Thomas, BA

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Maria Garris, BA

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Edward C. Frackelton, BA

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • F. George Otieno, MSc

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Rosetta M. Chiavacci, BSN

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Hyun-Duck Nah, PhD

      Affiliations

    • Division of Plastic Surgery, School of Medicine, University of Pennsylvania and Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Richard E. Kirschner, MD

      Affiliations

    • Division of Plastic Surgery, School of Medicine, University of Pennsylvania and Children's Hospital of Philadelphia, Philadelphia, PA
  • ,
  • Hakon Hakonarson, MD, PhD

      Affiliations

    • Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA
    • Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA
    • Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA

Received 18 March 2009; received in revised form 28 April 2009; accepted 11 June 2009. published online 05 August 2009.

Objective

To identify, in a non-hypothesis manner, novel genetic factors associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P).

Study design

We performed a genome-wide association study in a pediatric cohort of European decent consisting of 111 NSCL/P cases and 5951 control subjects. All subjects were consecutively recruited from the Greater Philadelphia area from 2006 to 2009. High throughput genome-wide single nucleotide polymorphism genotyping was carried out with the Illumina Infinium II HumanHap550 BeadChip technology.

Results

We observed association at the genome-wide significance level with SNP rs987525 at a locus on 8q24, which harbors no characterized genes to date (P = 9.18 × 10−8; odds ratio = 2.09, 95% confidence interval = 1.59 to 2.76). While searching for a replication cohort, the same genetic determinant was established through a genome-wide association study of NSCL/P in Germany, so this previous report acts as a de novo replication for our independent observation outlined here.

Conclusions

These results strongly suggest that a locus on 8q24 is involved in the pathogenesis of NSCL/P.

NSCL/P, Nonsyndromic cleft lip with or without cleft palate, OR, Odds ratio, SNP, Single nucleotide polymorphism

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 This research was financially supported by the Children's Hospital of Philadelphia and in part by a Research Development Award from the Cotswold Foundation (H.H. & S.F.A.G). The authors declare no conflicts of interest.

PII: S0022-3476(09)00575-7

doi:10.1016/j.jpeds.2009.06.020

The Journal of Pediatrics
Volume 155, Issue 6 , Pages 909-913, December 2009