%0 Journal Article
%T Testing Maternal-fetal Genotype Incompatibility With Mother-offspring Pair Data - Testing Maternal-fetal Genotype Incompatibility With Mother-offspring Pair Data - Open Access Pub
%A Kelian Sun
%A Ming Li
%A Minping Qian
%A Roberto Romero
%A Wenjiang J. Fu
%A Yuehua Cui
%J OAP | Home | Journal of Proteomics and Genomics Research | Open Access Pub
%D 2018
%X Maternal-fetal genotype (MFG) incompatibility has been shown to be strongly associated with a number of genetic diseases. Most current methods for the MFG test rely on parents-offspring trio genotype data and do not apply to mother-offspring pair data where paternal genotype is unavailable. In this paper, we developed a two-stage method for testing the allelic effect of given SNP through subgroup analysis of compatible MFG pairs and further tested the MFG incompatibility effect according to different scenarios determined by the allelic effect. Simulation studies demonstrated that this novel two-stage model is powerful in detecting the MFG incompatibility effect. This method can be implemented through publicly available statistical software, such as SAS, R, etc. We demonstrate with a case-control study of small for gestational age neonates that the method identified a SNP in the IGF2R gene with a significant allelic effect (p = 0.037), and a SNP in the IGF1 gene with a significant MFG incompatibility effect (OR = 0.75 and p = 0.033). DOI10.14302/issn.2326-0793.jpgr-12-160 Single nucleotide polymorphisms (SNPs) have been shown with growing evidence to be associated with many diseases through polymorphisms at single locus or through haplotype at multiple loci (Zhang et al. 2004, Spinka et al. 2004, Cui et al. 2007).43,37,9. Pediatric studies have demonstrated strong association of phenotypes or childhood diseases with parental genotypes, offspring genotypes or both (Goddard et al. 2007 and references therein)14 . In addition, research using both maternal and perinatal genotype data focusing on the interaction between the maternal and offspring genes has provided further evidence in gene-gene interaction, in particular, the effect of genotype incompatibility between the maternal and fetal genes has been found to play a critical role (Sinsheimer, Elston and Fu 2011). Hence searching for genes of incompatible maternal-fetal genotypes (MFG) is of particular interest. Studies of the incompatibility of MFG can be traced back to as early as 1960s on hemolytic disease of newborn caused by anti-K antibody (Kulich V, Kout M. 1967)19 and neonatal thrombopenia feto maternal incompatibility in human leukocytes antigen (HL-A) system (Salet et al. 1973a and 1973b)33,34. However, not until 1990s had the MFG received much attention (Hollister et al 1996). Although early studies introduced the MFG concept in human diseases research (Kulich V, Kout M. 1967, Salet et al. 1973a and 1973b, Stubbs, Ritvo and Mason-Brothers 1985)33,34,19,38 , statistical modeling of the MFG was
%U https://www.openaccesspub.org/jpgr/article/49