Healy Jasmine, Bourgey Mathieu, Richer Chantal, Sinnett Daniel, Roy-Gagnon Marie-Helene
Sainte-Justine Hospital Research Center, University of Montreal, Montreal, QC, Canada H3T 1C5.
J Biomed Biotechnol. 2010;2010:369534. doi: 10.1155/2010/369534. Epub 2010 Jun 9.
Several designs and analytical approaches have been proposed to dissect offspring from maternal genetic contributions to early-onset 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 for maternal 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.
已经提出了几种设计和分析方法来区分母体遗传因素对早发性疾病的子代影响。然而，缺乏亲代对照阻碍了对评估母体介导效应所需的交配对称性（MS）假设的直接验证。在本研究中，我们使用模拟来研究在对照的亲代缺失时，现有方法在交配不对称（MA）情况下的性能。我们的结果表明，即使在MA情况下，使用病例三联体/病例对照混合设计的对数线性、基于似然的框架也能为母体遗传效应提供有效的检验。使用这种方法，我们研究了12个细胞周期基因中的29个单核苷酸多态性（SNP）与儿童前B细胞急性淋巴细胞白血病（ALL）之间的母胎关联。我们在CDKN2A rs36228834位点（P = 0.017）和CDKN2B rs36229158位点（P = 0.022）发现了假定的母胎效应，这些效应调节了儿童ALL的风险。这些数据进一步证实了母亲的基因型对早发性疾病易感性的重要性。
