title: Testing for non-random mating: evidence for ancestry-related assortative mating in the Framingham heart study.
abstract: Population stratification leads to a predictable phenomenon-a reduction in the number of heterozygotes compared to that calculated assuming Hardy-Weinberg Equilibrium (HWE). We show that population stratification results in another phenomenon-an excess in the proportion of spouse-pairs with the same genotypes at all ancestrally informative markers, resulting in ancestrally related positive assortative mating. We use principal components analysis to show that there is evidence of population stratification within the Framingham Heart Study, and show that the first principal component correlates with a North-South European cline. We then show that the first principal component is highly correlated between spouses (r = 0.58, p = 0.0013), demonstrating that there is ancestrally related positive assortative mating among the Framingham Caucasian population. We also show that the single nucleotide polymorphisms loading most heavily on the first principal component show an excess of homozygotes within the spouses, consistent with similar ancestry-related assortative mating in the previous generation. This nonrandom mating likely affects genetic structure seen more generally in the North American population of European descent today, and decreases the rate of decay of linkage disequilibrium for ancestrally informative markers.
authors.affiliation: Institute for Human Genetics, University of California San Francisco, San Francisco, California 94143-0794, USA. rsebro@radmail.ucsf.edu
authors.forename: Ronnie
authors.initials: R
authors.lastname: Sebro
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hoffman
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
authors.forename: John J
authors.initials: JJ
authors.lastname: Rogus
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Risch
mesh_terms: D000483:Alleles; D005260:Female; D005787:Gene Frequency; D006331:Heart Diseases / Q000453:epidemiology / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008957:Models, Genetic; D017720:Molecular Epidemiology; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D018454:Spouses; D044465:White People / Q000235:genetics