Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Haplotype sharing provides insights into fine-scale population history and disease in Finland

View ORCID ProfileAlicia R. Martin, Konrad J. Karczewski, Sini Kerminen, Mitja Kurki, Antti-Pekka Sarin, Mykyta Artomov, Johan G. Eriksson, Tõnu Esko, Giulio Genovese, Aki S. Havulinna, Jaakko Kaprio, Alexandra Konradi, László Korányi, Anna Kostareva, Minna Männikkö, Andres Metspalu, Markus Perola, Rashmi B. Prasad, Olli Raitakari, Oxana Rotar, Veikko Salomaa, Leif Groop, Aarno Palotie, Benjamin M. Neale, Samuli Ripatti, Matti Pirinen, Mark J. Daly
doi: https://doi.org/10.1101/200113
Alicia R. Martin
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
2Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
3Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alicia R. Martin
Konrad J. Karczewski
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
2Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sini Kerminen
4Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mitja Kurki
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
2Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
3Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
5Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Antti-Pekka Sarin
4Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
6National Institute for Health and Welfare of Finland (THL), Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mykyta Artomov
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
2Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
3Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Johan G. Eriksson
6National Institute for Health and Welfare of Finland (THL), Helsinki, Finland
7Folkhälsan Research Center, Helsinki, Finland
8Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tõnu Esko
2Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
9Estonian Genome Center, University of Tartu, Tartu, Estonia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giulio Genovese
2Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
3Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aki S. Havulinna
4Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
6National Institute for Health and Welfare of Finland (THL), Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jaakko Kaprio
4Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
10Department of Public Health, University of Helsinki, Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexandra Konradi
11Almazov National Medical Research Centre, Saint Petersburg, Russia
12ITMO University, Saint Petersburg, Russia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
László Korányi
13Heart Center Foundation, DRC, Balatonfured, Hungary
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna Kostareva
11Almazov National Medical Research Centre, Saint Petersburg, Russia
12ITMO University, Saint Petersburg, Russia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Minna Männikkö
14Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andres Metspalu
9Estonian Genome Center, University of Tartu, Tartu, Estonia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Markus Perola
4Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
9Estonian Genome Center, University of Tartu, Tartu, Estonia
15Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku University Hospital, Turku, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rashmi B. Prasad
17Lund University Diabetes Centre, Department of Clinical Sciences, Lund University CRC, Skåne University Hospital Malmö, SE-205 02, Malmö, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olli Raitakari
15Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku University Hospital, Turku, Finland
16Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Oxana Rotar
11Almazov National Medical Research Centre, Saint Petersburg, Russia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Veikko Salomaa
6National Institute for Health and Welfare of Finland (THL), Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leif Groop
4Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
17Lund University Diabetes Centre, Department of Clinical Sciences, Lund University CRC, Skåne University Hospital Malmö, SE-205 02, Malmö, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aarno Palotie
2Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
3Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
4Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
5Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benjamin M. Neale
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
2Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
3Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Samuli Ripatti
4Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
10Department of Public Health, University of Helsinki, Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matti Pirinen
4Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
10Department of Public Health, University of Helsinki, Helsinki, Finland
18Helsinki Institute for Information Technology HIIT and Department of Mathematics and Statistics, University of Helsinki, 00014 Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark J. Daly
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
2Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
3Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
4Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted October 13, 2017.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Haplotype sharing provides insights into fine-scale population history and disease in Finland
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Haplotype sharing provides insights into fine-scale population history and disease in Finland
Alicia R. Martin, Konrad J. Karczewski, Sini Kerminen, Mitja Kurki, Antti-Pekka Sarin, Mykyta Artomov, Johan G. Eriksson, Tõnu Esko, Giulio Genovese, Aki S. Havulinna, Jaakko Kaprio, Alexandra Konradi, László Korányi, Anna Kostareva, Minna Männikkö, Andres Metspalu, Markus Perola, Rashmi B. Prasad, Olli Raitakari, Oxana Rotar, Veikko Salomaa, Leif Groop, Aarno Palotie, Benjamin M. Neale, Samuli Ripatti, Matti Pirinen, Mark J. Daly
bioRxiv 200113; doi: https://doi.org/10.1101/200113
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Haplotype sharing provides insights into fine-scale population history and disease in Finland
Alicia R. Martin, Konrad J. Karczewski, Sini Kerminen, Mitja Kurki, Antti-Pekka Sarin, Mykyta Artomov, Johan G. Eriksson, Tõnu Esko, Giulio Genovese, Aki S. Havulinna, Jaakko Kaprio, Alexandra Konradi, László Korányi, Anna Kostareva, Minna Männikkö, Andres Metspalu, Markus Perola, Rashmi B. Prasad, Olli Raitakari, Oxana Rotar, Veikko Salomaa, Leif Groop, Aarno Palotie, Benjamin M. Neale, Samuli Ripatti, Matti Pirinen, Mark J. Daly
bioRxiv 200113; doi: https://doi.org/10.1101/200113

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3586)
  • Biochemistry (7545)
  • Bioengineering (5495)
  • Bioinformatics (20730)
  • Biophysics (10294)
  • Cancer Biology (7950)
  • Cell Biology (11610)
  • Clinical Trials (138)
  • Developmental Biology (6586)
  • Ecology (10168)
  • Epidemiology (2065)
  • Evolutionary Biology (13578)
  • Genetics (9520)
  • Genomics (12817)
  • Immunology (7906)
  • Microbiology (19503)
  • Molecular Biology (7641)
  • Neuroscience (41982)
  • Paleontology (307)
  • Pathology (1254)
  • Pharmacology and Toxicology (2192)
  • Physiology (3259)
  • Plant Biology (7018)
  • Scientific Communication and Education (1293)
  • Synthetic Biology (1947)
  • Systems Biology (5418)
  • Zoology (1113)