title: The genome-wide patterns of variation expose significant substructure in a founder population.
abstract: Although high-density SNP genotyping platforms generate a momentum for detailed genome-wide association (GWA) studies, an offshoot is a new insight into population genetics. Here, we present an example in one of the best-known founder populations by scrutinizing ten distinct Finnish early- and late-settlement subpopulations. By determining genetic distances, homozygosity, and patterns of linkage disequilibrium, we demonstrate that population substructure, and even individual ancestry, is detectable at a very high resolution and supports the concept of multiple historical bottlenecks resulting from consecutive founder effects. Given that genetic studies are currently aiming at identifying smaller and smaller genetic effects, recognizing and controlling for population substructure even at this fine level becomes imperative to avoid confounding and spurious associations. This study provides an example of the power of GWA data sets to demonstrate stratification caused by population history even within a seemingly homogeneous population, like the Finns. Further, the results provide interesting lessons concerning the impact of population history on the genome landscape of humans, as well as approaches to identify rare variants enriched in these subpopulations.
authors.affiliation: Department of Molecular Medicine, National Public Health Institute and Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
authors.forename: Eveliina
authors.initials: E
authors.lastname: Jakkula
authors.forename: Karola
authors.initials: K
authors.lastname: Rehnström
authors.forename: Teppo
authors.initials: T
authors.lastname: Varilo
authors.forename: Olli P H
authors.initials: OP
authors.lastname: Pietiläinen
authors.forename: Tiina
authors.initials: T
authors.lastname: Paunio
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.forename: Ulf
authors.initials: U
authors.lastname: deFaire
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.forename: Juha
authors.initials: J
authors.lastname: Saharinen
authors.forename: Nelson
authors.initials: N
authors.lastname: Freimer
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Shaun
authors.initials: S
authors.lastname: Purcell
authors.forename: Andrew
authors.initials: A
authors.lastname: Collins
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000483:Alleles; D002892:Chromosomes, Human, Pair 22; D018703:Founder Effect; D005787:Gene Frequency; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D011153:Population