对数线性模型在病例-父母/对照-母亲混合设计中的应用

以唇腭裂与亚甲基四氢叶酸还原酶(MTHFR)基因A1298C多样性的关系为例,基于似然比检验(LRT)的对数线性模型分析母亲、子代基因型与唇腭裂的关系,介绍应用对数线性模型分析病例-父母/对照-母亲混合设计资料的方法应用。发现母亲基因型为CC时,相对于基因型为AA的母亲,其子代唇腭裂发病风险降低,S₂=0.45(95%CI:0.26~0.79);子代基因型为AC时,相对于AA其发病风险降低,R₁=0.69(95%CI:0.48~0.97),其余未见关联。混合设计的效力要大于病例-父母对照研究(0.86>0.78)。表明MTHFR A1298C可能在唇腭裂的病因学机制中起重要作用。应用对数线性模型对这类混合设计资料的分析可以同时探讨母亲、子代基因型对疾病的影响,且相对病例-父母对照研究效力更高,适用于出生缺陷等生命早期疾病的病因学研究。

Log-linear model used in the hybrid design of case-parents triad/control-mother dyad

This study introduced the application of a log-linear model in the hybrid design of case-parents triad/control-mother dyad. Data related to the association between cleft lip with palate (CLP) and methylenetetrahydrofolate reductase (MTHFR) gene A1298C diversity was analyzed. Log-linear model based on likelihood ratio tests (LRTs) was used to analyze the relationships between mother, offspring genotypes and CLP. Data from our study noticed that children of mothers carrying the CC genotype presented a lower risk of CLP, comparing with the children of mothers carrying the AA genotype, with S₂=0.45 (95%CI:0.26-0.79). Offspring that carrying the AC genotype presented a lower risk of CLP, comparing with the offspring that carrying the AA genotype, with R₁=0.69 (95%CI:0.48-0.97). However, no other types of relationships were found. The power of hybrid design was greater than the case-parents study (0.86>0.78). MTHFR A1298C polymorphism seemed to have played an important role in the etiology on both cleft lip and palate. Data from the hybrid design and the log-linear model could help researchers to explore the effects of genotypes from both mothers and the offspring. This study design would present stronger power than the regular case-parents studies thus suitable for studies on the etiology of diseases in early lives, as birth defects.