Abstract
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.
Highlights
The mating pattern determines the genetic structure of a population [1, 2, 3]
We showed that the mating pattern results in Hardy-Weinberg disequilibrium (HWD) at ancestrally-informative single nucleotide polymorphisms (SNPs), and results in linkage disequilibrium (LD) between unlinked loci
We investigate the degree to which the genotypic consequences of spouse assortment for height is primarily due to the effect of the contributing SNPs on height versus their correlation with genetic ancestry in the Framingham Heart Study (FHS) original, offspring and third generation cohorts
Summary
The mating pattern determines the genetic structure of a population [1, 2, 3]. The genetic structure of a population refers to the distribution of alleles and genotypes in the population. Population substructure can arise in a study population from geographic stratification and/ or non-random mating. Geographic stratification occurs when the study participants are recruited from different geographic areas, and the genotype data is aggregated for analysis. In this setting, there may be random mating within each geographic subgroup, there is non-random mating within the aggregated study population. Population substructure can occur when the study participants are recruited from the same geographic area but individuals are more likely to choose mates with similar genotypes to themselves–which can be a reflection of trait-based or ancestry-related assortative mating [9, 10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
