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Open Access Methodology article

Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism

Steven Buyske1*, Tanishia A Williams2, Audrey E Mars34, Edward S Stenroos2, Sue X Ming456, Rong Wang2, Madhura Sreenath2, Marivic F Factura3, Chitra Reddy5, George H Lambert34 and William G Johnson24

Author Affiliations

1 Departments of Statistics and Genetics, 110 Frelinghuysen Rd, Rutgers University, Piscataway, NJ 08854, USA

2 Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA

3 Department of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA

4 Center for Childhood Neurotoxicology & Exposure Assessment, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA

5 Department of Pediatrics, UMDNJ New Jersey Medical School, 90 Bergen Street, Newark, NJ 07103, USA

6 Department of Neuroscience, UMDNJ New Jersey Medical School, 90 Bergen Street, Newark, NJ 07103, USA

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BMC Genetics 2006, 7:8  doi:10.1186/1471-2156-7-8

Published: 10 February 2006

Abstract

Background

Certain loci on the human genome, such as glutathione S-transferase M1 (GSTM1), do not permit heterozygotes to be reliably determined by commonly used methods. Association of such a locus with a disease is therefore generally tested with a case-control design. When subjects have already been ascertained in a case-parent design however, the question arises as to whether the data can still be used to test disease association at such a locus.

Results

A likelihood ratio test was constructed that can be used with a case-parents design but has somewhat less power than a Pearson's chi-squared test that uses a case-control design. The test is illustrated on a novel dataset showing a genotype relative risk near 2 for the homozygous GSTM1 deletion genotype and autism.

Conclusion

Although the case-control design will remain the mainstay for a locus with a deletion, the likelihood ratio test will be useful for such a locus analyzed as part of a larger case-parent study design. The likelihood ratio test has the advantage that it can incorporate complete and incomplete case-parent trios as well as independent cases and controls. Both analyses support (p = 0.046 for the proposed test, p = 0.028 for the case-control analysis) an association of the homozygous GSTM1 deletion genotype with autism.