Structured mating: Patterns and implications

Genetic similarity of spouses can reflect factors influencing mate choice, such as physical/behavioral characteristics, and patterns of social endogamy. Spouse correlations for both genetic ancestry and measured traits may impact genotype distributions (Hardy Weinberg and linkage equilibrium), and therefore genetic association studies. Here we evaluate white spouse-pairs from the Framingham Heart Study (FHS) original and offspring cohorts (N = 124 and 755, respectively) to explore spousal genetic similarity and its consequences. Two principal components (PCs) of the genome-wide association (GWA) data were identified, with the first (PC1) delineating clines of Northern/Western to Southern European ancestry and the second (PC2) delineating clines of Ashkenazi Jewish ancestry. In the original (older) cohort, there was a striking positive correlation between the spouses in PC1 (r = 0.73, P = 3x10-22) and also for PC2 (r = 0.80, P = 7x10-29). In the offspring cohort, the spouse correlations were lower but still highly significant for PC1 (r = 0.38, P = 7x10-28) and for PC2 (r = 0.45, P = 2x10-39). We observed significant Hardy-Weinberg disequilibrium for single nucleotide polymorphisms (SNPs) loading heavily on PC1 and PC2 across 3 generations, and also significant linkage disequilibrium between unlinked SNPs; both decreased with time, consistent with reduced ancestral endogamy over generations and congruent with theoretical calculations. Ignoring ancestry, estimates of spouse kinship have a mean significantly greater than 0, and more so in the earlier generations. Adjusting kinship estimates for genetic ancestry through the use of PCs led to a mean spouse kinship not different from 0, demonstrating that spouse genetic similarity could be fully attributed to ancestral assortative mating. These findings also have significance for studies of heritability that are based on distantly related individuals (kinship less than 0.05), as we also demonstrate the poor correlation of kinship estimates in that range when ancestry is or is not taken into account.Author summary: We analyzed three generations of whites from the Framingham Heart Study (FHS) using genome-wide genotype data to characterize their genetic ancestry. By examination of spouse-pairs, we observed that individuals of Northern/Western European, Southern European and Ashkenazi ancestry preferentially chose spouses of the same ancestry, however, the degree of endogamy decreased in each successive generation, especially between Northern/Western and Southern Europeans. We then showed that the mating pattern results in Hardy-Weinberg disequilibrium (HWD) at ancestrally-informative SNPs, and also results in linkage disequilibrium (LD) between unlinked loci. The HWD and LD decrease as theoretically expected with the decrease in endogamy noted in each generation. In the FHS sample, spouse genetic similarity can be explained by ancestry-related assortative mating.