Biology subjects

Hansen, T. F.

Publications and source records attributed to Hansen, T. F..

7 recordsLinked to original sources

bioRxiv2026

Genomic impact of the second plague pandemic on three human populations

The second plague pandemic (early 14th-early 19th centuries), which was caused by Yersinia pestis, had a profound demographic, socio-economic and cultural impact across Eurasia and North Africa. Many regions in Europe and the Middle East are estimated to have lost 40-60% of their human populations, with some areas suffering even higher mortality. Whether exposure to Y. pestis drove strong positive selection on protective genetic variants in the human genome, and how it shaped migration patterns, remains debated, despite several recent studies based on ancient DNA. Here, we analyse a markedly larger, higher coverage, and geographically diverse dataset based on shotgun sequencing of genomes from 529 ancient individuals to a mean depth 8.8x dating to either before or after the arrival of the pandemic at three sites in northern Europe: Trondheim (Norway), Lund (Sweden) and Vilnius (Lithuania). Genome-wide scans for signatures of selection provide no evidence for strong positive selection acting on specific genetic variants driven by Y. pestis exposure: we neither replicate selection signatures reported by previous studies nor identify new genome-wide significant candidates. However, for all three sites, we observe evidence for a reduction in long-range immigration, indicated by a drop in the diversity of ancestry that followed the arrival of Y. pestis and broadly coincided with the end of the Viking Age, Christianisation and the onset of the Little Ice Age. Our results shed important light on the demographic impact of major sociohistorical changes that occurred during the late Medieval period in Scandinavia and the Baltic region and link Christianisation to increased diversity in ancestry before the pandemic.

genomics↗

bioRxiv2025

Protein tyrosine phosphatase receptor type D - A convergent risk gene for MDD, BPD, and ADHD and regulator of dopaminergic neuroplasticity in reward associated circuits; A multivariate GWAS, brain tissue and cell type enrichment, and gene finemapping

Major depressive disorder (MDD), bipolar disorder (BPD), and attention-deficit hyperactivity disorder (ADHD), are prevalent, highly heritable psychiatric disorders with significant degrees of genetic overlap. Using open-sourced summary statistics from the Psychiatric Genomics Consortium and 1000 Genomes European reference panel, we utilize a plethora of statistical frameworks to estimate shared genetic liability across MDD, BPD, and ADHD. We observed significant enrichment of latent genetic variables in dopamine neurons, and identify protein tyrosine phosphatase receptor delta (PTPRD), as a candidate gene. Literature review and gene fine-mapping suggest that PTPRD indirectly regulates DAT transporter surface trafficking and neuronal excitability. We propose that the loss of PTPRDs D1 phosphatase domain results in hyperactivated tropomyosin receptor kinase B (TrkB) and rearranged during transfection proto-oncogene tyrosine-protein kinase receptor (RET) signaling in dopamine neurons, potentiating excessive downstream phosphorylation and activation of VAV2, ERK1/2, and PKC. We hypothesize that these mechanisms contribute to the significantly altered reward-related behaviors such as cocaine-conditioned place preference, cocaine self-administration, motivation for cocaine, and goal oriented behavior that are consistently observed across PTPRD KO/inhibition mice studies. With the inclusion of literature review, we present the first integrated multivariate genetic and mechanistic analysis aimed to identify pleiotropic, cell type-specific mechanisms driving psychiatric comorbidity at the biochemical level.

genomics↗

bioRxiv2025

Population-scale analysis of inheritance patterns across 858,635 individuals reveals recent historical migration patterns across the North Sea from the Middle Ages to the Industrial Revolution

The North Seas historical migrations have impacted the genetic structure of its neighbouring populations. We analysed haplotype sharing among 858,635 modern individuals from Denmark and Britain to infer migration history from the Middle Ages to the modern day. We estimated the genetic relationship among 370,259 Danes using Danish healthcare registries and validated those with retrievable pedigree relationships from a national family registry. We also compared their haplotype sharing with 488,376 British individuals from the UK Biobank. Our analysis revealed the fine-grained population genetic history of Denmark and identified distinct coastal and island communities with a history of genetic isolation and bottlenecks. We observed a significant population decline in Jutland compared to Zealand from the late medieval period to the start of early modern period, accompanied by migration from Jutland to Zealand, corresponding to historical evidence. We identified two major haplotype sharing patterns between Denmark and Great Britain: (1) early coast-to-coast connections between South Jutland and eastern England, likely driven by migration, settlement, continuous trade and the movement of people across the North Sea from the Middle Ages through early modern times, and (2) later city-to-city connections such as those between London and Kobenhavn, likely shaped by the reorientation of economic and trading centres in Britain and Denmark, and the increased shipping from early modern times towards the Industrial Revolution. Further comparisons using other North Sea countries showed both shared and unique histories of genetic exchange with Denmark and Britain. Our study provides novel genetic evidence of migration across the North Sea from the Middle Ages to the Industrial Revolution. It highlights the power of nationwide biobanks in reconstructing fine-scale historical population movements among closely related populations.

genetics↗

bioRxiv2020

Fly wing evolutionary rate is a near-isometric function of mutational variation

If there is abundant mutational and standing genetic variation, most expect that the rate of evolution would be driven primarily by natural selection, and potentially be independent of current variability or variation. Contrary to this expectation, we (H17: Houle et al. 2017 Nature 548:447) found surprisingly strong scaling relationships with slopes near one between mutational variance, standing genetic variance and macro-evolutionary rate in Drosophilid wing traits. Jiang and Zhang (J&Z20: 2020 Evolution https://doi.org/10.1111/evo.14076) have challenged these results and our interpretation of them. J&Z20 showed that the method used in H17 to estimate the scaling relationship between variation at different biological levels is uninformative. Using an alternative method, they estimated that the scaling relationship has a slope substantially less than one, and propose a variant of our neutral subset hypothesis to explain this. Here we use simulations to confirm J&Z20s finding that the H17 method for estimating scaling of variances is uninformative. The simulations also show their alternative method for estimating scaling is likely to be seriously biased towards lower scaling relationships. We propose and verify an alternative approach to calculating scaling relationships based on independently estimated variance matrices, which we call the Q method. Simulations and reanalyses of the Drosophilid data set using the Q method suggests that our original estimates of the scaling relationship were close to the true value. We propose an analytical version of the neutral subset model, and show that it can indeed explain any scaling slope by varying assumptions about the pattern of pleiotropy. We continue to regard neutral subset models as implausible for wing shape in Drosophilids due to the likelihood that wing shape is subject to direct selection. Hybrid models in which pleiotropy reduces the available genetic and mutational variation, and a combination of selection and drift controls the change in species means seem more biologically promising.

evolutionary biology↗

bioRxiv2020

The genetic structure of Norway

The aim of the present study was to describe the genetic structure of the Norwegian population using genotypes from 6369 unrelated individuals with detailed information about places of residence. Using standard single marker- and haplotype-based approaches, we report evidence of two regions with distinctive patterns of genetic variation, one in the far northeast, and another in the south of Norway, as indicated by fixation indices, haplotype sharing, homozygosity and effective population size. We detect and quantify a component of Uralic Sami ancestry that is enriched in the North. On a finer scale, we find that rates of migration have been affected by topography like mountain ridges. In the broader Scandinavian context, we detect elevated relatedness between the mid- and northern border areas towards Sweden. The main finding of this study is that despite Norways long maritime history and as a former Danish territory, the region closest to mainland Europe in the south appears to have been the most isolated region in Norway, highlighting the open sea as a barrier to gene flow.

genetics↗

bioRxiv2020

Changes in the gene expression profile during spontaneous migraine attacks

ObjectiveMigraine occurs in clearly defined attacks and thus lends itself to investigate changes during and outside attack. Gene expression fluctuates according to environmental and endogenous events and therefore is likely to reveal changes during a migraine attack. We examined the hypothesis that changes in RNA expression during and outside of a spontaneous migraine attack exist which are specific to the migraine attack. MethodsWe collected blood samples from 27 migraine patients during an attack, two hours after treatment with subcutaneous sumatriptan, on a headache-free day and after a cold pressor test. All patients were deeply phenotyped, including headache characteristics and treatment effect during the sampling. RNA-Sequencing, genotyping, and steroid profiling was performed on all samples. RNA-Sequences were analyzed at gene level (differential expression analysis) and at network level, and we integrated transcriptomic and genomic data. ResultsWe found 29 differentially expressed (DE) genes between attack and after treatment, after subtracting non-migraine specific genes, i.e. genes related to a general pain/stress response. DE genes were functioning in fatty acid oxidation, signaling pathways and immune-related pathways. Network analysis revealed molecular mechanisms affected by change in gene interactions during the migraine attack, e.g. ion transmembrane transport and response to stress. Integration of genomic and transcriptomic data revealed pathways related to sumatriptan treatment, i.e. 5HT1 type receptor mediated signaling pathway. InterpretationUsing a paired-sample design, we uniquely investigated intra-individual changes in the gene expression during a migraine attack. We revealed both genes and pathway potentially involved in the pathophysiology of migraine.

genomics↗

bioRxiv2019

Genome-wide association study identifies 49 common genetic variants associated with handedness.

Handedness, a consistent asymmetry in skill or use of the hands, has been studied extensively because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and 32 studies from the International Handedness Consortium, we conducted the worlds largest genome-wide association study of handedness (1,534,836 right-handed, 194,198 (11.0%) left-handed and 37,637 (2.1%) ambidextrous individuals). We found 41 genetic loci associated with left-handedness and seven associated with ambidexterity at genome-wide levels of significance (P < 5x10-8). Tissue enrichment analysis implicated the central nervous system and brain tissues including the hippocampus and cerebrum in the etiology of left-handedness. Pathways including regulation of microtubules, neurogenesis, axonogenesis and hippocampus morphology were also highlighted. We found suggestive positive genetic correlations between being left-handed and some neuropsychiatric traits including schizophrenia and bipolar disorder. SNP heritability analyses indicated that additive genetic effects of genotyped variants explained 5.9% (95% CI = 5.8% - 6.0%) of the underlying liability of being left-handed, while the narrow sense heritability was estimated at 12% (95% CI = 7.2% - 17.7%). Further, we show that genetic correlation between left-handedness and ambidexterity is low (rg = 0.26; 95% CI = 0.08 - 0.43) implying that these traits are largely influenced by different genetic mechanisms. In conclusion, our findings suggest that handedness, like many other complex traits is highly polygenic, and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders that has been observed in multiple observational studies.

genetics↗