학술논문
Detection of Fetomaternal Genotype Associations in Early-Onset Disorders: Evaluation of Different Methods and Their Application to Childhood Leukemia.
Document Type
Article
Source
Subject
*LEUKEMIA in children
*EARLY diagnosis
*LYMPHOBLASTIC leukemia in children
*SIMULATION methods & models
*VERTICAL transmission (Communicable diseases)
*COMMUNICABLE diseases
*GENOTYPE-environment interaction
*DIAGNOSIS
LEUKEMIA genetics
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Language
ISSN
1110-7243
Abstract
Several designs and analytical approaches have been proposed to dissect offspring from maternal genetic contributions to earlyonset diseases. However, lack of parental controls halts the direct verification of the assumption of mating symmetry (MS) required to assess maternally-mediated effects. In this study, we used simulations to investigate the performance of existing methods under mating asymmetry (MA) when parents of controls are missing. Our results show that the log-linear, likelihood-based framework using a case-triad/case-control hybrid design provides valid tests formaternal genetic effects even under MA. Using this approach, we examined fetomaternal associations between 29 SNPs in 12 cell-cycle genes and childhood pre-B acute lymphoblastic leukemia (ALL). We identified putative fetomaternal effects at loci CDKN2A rs36228834 (P = .017) and CDKN2B rs36229158 (P = .022) that modulate the risk of childhood ALL. These data further corroborate the importance of the mother's genotype on the susceptibility to early-onset diseases. [ABSTRACT FROM AUTHOR]