Identification of Two Maternal Transmission Ratio Distortion Loci in Pedigrees of the Framingham Heart Study

Transmission ratio distortion (TRD) is indicated by the recovery of alleles in offspring in non-Mendelian proportions. An assumption of Mendelian proportion is central to many methods to identify disease-associated markers. This seems reasonable as, while TRD cases have been occasionally observed in various species few instances have been identified in humans. Here we search for evidence of paternal or maternal TRD with genome-wide SNP data of pedigrees from the Framingham Heart Study. After excluding many examples as better explained by genotyping errors we identified two maternal-specific TRD loci for autosomal SNPs rs6733122 and rs926716 (corrected P = 0.029 and P = 0.018) on LRP2 and ZNF133, respectively. The transmission ratios were as high as 1.7~1.8:1. Genotyping validation and further replication is still necessary to confirm the TRD. This study shows that there may be large-effect maternal-specific TRD loci of common SNPs in the human genome but that these are rare.