The genome-wide patterns of variation expose significant substructure in a founder population.
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.
Jakkula
Eveliina
E
Department of Molecular Medicine, National Public Health Institute and Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
Rehnström
Karola
K
Varilo
Teppo
T
Pietiläinen
Olli P H
OP
Paunio
Tiina
T
Pedersen
Nancy L
NL
deFaire
Ulf
U
Järvelin
Marjo-Riitta
MR
Saharinen
Juha
J
Freimer
Nelson
N
Ripatti
Samuli
S
Purcell
Shaun
S
Collins
Andrew
A
Daly
Mark J
MJ
Palotie
Aarno
A
Peltonen
Leena
L
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