Parental genotypes in the risk of a complex disease.
Our understanding of the genetic etiology of complex disorders is still elusive. According to the common-variant/common-disease hypothesis, frequent functional polymorphisms are the best candidates for disease-susceptibility alleles. Implicitly, we also assume that disease-susceptibility alleles are preferentially transmitted from parents to the affected offspring and that this effect can be captured by the transmission/disequilibrium test (TDT). However, our study of genetic predisposition to childhood acute lymphoblastic leukemia suggests that a focus on the patient's genotype might, in certain instances, be misleading. Our results indicate that, at least at some loci, parental genetics might be of primary importance in predicting the risk of cancer in this pediatric model of a complex disease. Consequently, in addition to TDT, other complementary strategies will need to be simultaneously applied to dissect genetic predisposition to complex disorders.
Labuda
Damian
D
Centre de recherche, Hôpital Sainte Justine, Université de Montréal, Québec, H3T 1C5 Canada. damian.labuda@umontreal.ca
Krajinovic
Maja
M
Sabbagh
Audrey
A
Infante-Rivard
Claire
C
Sinnett
Daniel
D
D016022:Case-Control Studies; D002648:Child; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008957:Models, Genetic; D010290:Parents; D010375:Pedigree; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics*; D012307:Risk Factors
D007527:Isoenzymes; D019392:Cytochrome P-450 CYP2E1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase