RT Journal Article
SR Electronic
T1 Haplotype sharing provides insights into fine-scale population history and disease in Finland
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 200113
DO 10.1101/200113
A1 Alicia R. Martin
A1 Konrad J. Karczewski
A1 Sini Kerminen
A1 Mitja Kurki
A1 Antti-Pekka Sarin
A1 Mykyta Artomov
A1 Johan G. Eriksson
A1 Tõnu Esko
A1 Giulio Genovese
A1 Aki S. Havulinna
A1 Jaakko Kaprio
A1 Alexandra Konradi
A1 László Korányi
A1 Anna Kostareva
A1 Minna Männikkö
A1 Andres Metspalu
A1 Markus Perola
A1 Rashmi B. Prasad
A1 Olli Raitakari
A1 Oxana Rotar
A1 Veikko Salomaa
A1 Leif Groop
A1 Aarno Palotie
A1 Benjamin M. Neale
A1 Samuli Ripatti
A1 Matti Pirinen
A1 Mark J. Daly
YR 2017
UL http://biorxiv.org/content/early/2017/10/13/200113.abstract
AB Finland provides unique opportunities to investigate population and medical genomics because of its adoption of unified national electronic health records, detailed historical and birth records, and serial population bottlenecks. We assemble a comprehensive view of recent population history (≤100 generations), the timespan during which most rare disease-causing alleles arose, by comparing pairwise haplotype sharing from 43,254 Finns to geographically and linguistically adjacent countries with different population histories, including 16,060 Swedes, Estonians, Russians, and Hungarians. We find much more extensive sharing in Finns, with at least one ≥ 5 cM tract on average between pairs of unrelated individuals. By coupling haplotype sharing with fine-scale birth records from over 25,000 individuals, we find that while haplotype sharing broadly decays with geographical distance, there are pockets of excess haplotype sharing; individuals from northeast Finland share several-fold more of their genome in identity-by-descent (IBD) segments than individuals from southwest regions containing the major cities of Helsinki and Turku. We estimate recent effective population size changes over time across regions of Finland and find significant differences between the Early and Late Settlement Regions as expected; however, our results indicate more continuous gene flow than previously indicated as Finns migrated towards the northernmost Lapland region. Lastly, we show that haplotype sharing is locally enriched among pairs of individuals sharing rare alleles by an order of magnitude, especially among pairs sharing rare disease causing variants. Our work provides a general framework for using haplotype sharing to reconstruct an integrative view of recent population history and gain insight into the evolutionary origins of rare variants contributing to disease.