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


CONCLUSIONS
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.
Buyske
Steven
S
Departments of Statistics and Genetics, 110 Frelinghuysen Rd, Rutgers University, Piscataway, NJ 08854, USA. buyske@stat.rutgers.edu
Williams
Tanishia A
TA
Mars
Audrey E
AE
Stenroos
Edward S
ES
Ming
Sue X
SX
Wang
Rong
R
Sreenath
Madhura
M
Factura
Marivic F
MF
Reddy
Chitra
C
Lambert
George H
GH
Johnson
William G
WG
D000328:Adult; D001321:Autistic Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008957:Models, Genetic
D005982:Glutathione Transferase