title: Structured mating: Patterns and implications.
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.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States of America.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Sebro
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Peloso
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America.|National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, United States of America.
authors.forename: Josée
authors.identifier: 0000-0003-2871-3603
authors.initials: J
authors.lastname: Dupuis
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, United States of America.|Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, United States of America.|Division of Research, Kaiser Permanente, Oakland, CA, United States of America.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Risch
mesh_terms: D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007585:Jews / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018454:Spouses; D044465:White People / Q000235:genetics*