Department of Economics and Business Economics

Complex spatio-temporal distribution and genomic ancestry of mitochondrial DNA haplogroups in 24,216 Danes

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  • Jonas Bybjerg-Grauholm, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;
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  • Christian M Hagen, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;
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  • Vanessa F Gonçalves, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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  • Marie Bækvad-Hansen, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;
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  • Christine S Hansen, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;
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  • Paula L Hedley, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;
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  • Jørgen K Kanters
  • Jimmi Nielsen, Unit for Psychiatric Research, Aalborg Psychiatric Hospital, Aalborg University Hospital, Aalborg, Denmark
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  • Michael Theisen, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;
  • ,
  • Ole Mors
  • James Kennedy, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • ,
  • Thomas D Als
  • Alfonso B Demur, Mental Health Centre Sct. Hans, Capital Region of Denmark, Institute of Biological Psychiatry, Copenhagen University Hospital, Copenhagen, Denmark.
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  • Merete Nordentoft, Mental Health Centre Copenhagen, Copenhagen University Hospital, Mental Health Services Capital Region, Hellerup, Denmark
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  • Anders Børglum
  • Preben B Mortensen
  • Thomas M Werge, Mental Health Centre Sct. Hans, Capital Region of Denmark, Institute of Biological Psychiatry, Copenhagen University Hospital, Copenhagen, Denmark.
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  • David M Hougaard, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;
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  • Michael Christiansen, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;, Department of Cardiology , Rigshospitalet , Copenhagen, Denmark ; Department of Biomedical Sciences , Copenhagen University , Copenhagen , Denmark.

Mitochondrial DNA (mtDNA) haplogroups (hgs) are evolutionarily conserved sets of mtDNA SNP-haplotypes with characteristic geographical distribution. Associations of hgs with disease and physiological characteristics have been reported, but have frequently not been reproducible. Using 418 mtDNA SNPs on the PsychChip (Illumina), we assessed the spatio-temporal distribution of mtDNA hgs in Denmark from DNA isolated from 24,642 geographically un-biased dried blood spots (DBS), collected from 1981 to 2005 through the Danish National Neonatal Screening program. ADMIXTURE was used to establish the genomic ancestry of all samples using a reference of 100K+ autosomal SNPs in 2,248 individuals from nine populations. Median-joining analysis determined that the hgs were highly variable, despite being typically Northern European in origin, suggesting multiple founder events. Furthermore, considerable heterogeneity and variation in nuclear genomic ancestry was observed. Thus, individuals with hg H exhibited 95%, and U hgs 38.2% - 92.5%, Danish ancestry. Significant clines between geographical regions and rural and metropolitan populations were found. Over 25 years, macro-hg L increased from 0.2% to 1.2% (p = 1.1*E-10), and M from 1% to 2.4% (p = 3.7*E-8). Hg U increased among the R macro-hg from 14.1% to 16.5% (p = 1.9*E-3). Genomic ancestry, geographical skewedness, and sub-hg distribution suggested that the L, M and U increases are due to immigration. The complex spatio-temporal dynamics and genomic ancestry of mtDNA in the Danish population reflect repeated migratory events and, in later years, net immigration. Such complexity may explain the often contradictory and population-specific reports of mito-genomic association with disease.

Original languageEnglish
Article numbere0208829
JournalPLOS ONE
Volume13
Issue12
ISSN1932-6203
DOIs
Publication statusPublished - 2018

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