RT Journal Article
SR Electronic
T1 Complex spatio-temporal distribution and genogeographic affinity of mitochondrial DNA haplogroups in 24,216 Danes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 148494
DO 10.1101/148494
A1 Jonas Bybjerg-Grauholm
A1 Christian M Hagen
A1 Vanessa F Gonçalves
A1 Marie Bækvad-Hansen
A1 Christine S Hansen
A1 Paula L Hedley
A1 Jørgen K Kanters
A1 Jimmi Nielsen
A1 Michael Theisen
A1 Ole Mors
A1 James Kennedy
A1 Thomas D Als
A1 Alfonso B Demur
A1 Thomas M Werge
A1 Merete Nordentoft
A1 Anders Børglum
A1 Preben Bo Mortensen
A1 David M Hougaard
A1 Michael Christiansen
YR 2017
UL http://biorxiv.org/content/early/2017/06/10/148494.abstract
AB 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 in DNA isolated from 24,642 geographically un-biased dried blood spots (DBS), collected from 1981 to 2005 through the Danish National Neonatal Screening program. Geno-geographic affinity (ancestry background) was established with ADMIXTURE using a reference of 100K+ autosomal SNPs in 2,248 individuals from nine populations. The hg distribution was typically Northern European, and hgs were highly variable based on median-joining analysis, suggesting multiple founder events. Considerable heterogeneity and variation in autosomal geno-geographic affinity 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). Geno-geographic affinity, geographical skewedness, and sub-hg distribution suggested that the L, M and U increases are due to immigration. The complex spatio-temporal dynamics and geno-geographic heterogeneity 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.