[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.