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After a long-distance migration, Avars with Eastern Asian ancestry arrived in Eastern Central Europe in 567 to 568 CE and encountered groups with very different European ancestry. We used ancient genome-wide data of 722 individuals and fine-grained interdisciplinary analysis of large seventh- to eighth-century CE neighbouring cemeteries south of Vienna (Austria) to address the centuries-long impact of this encounter. We found that even 200 years after immigration, the ancestry at one site (Leobersdorf) remained dominantly East Asian-like, whereas the other site (Mödling) shows local, European-like ancestry. These two nearby sites show little biological relatedness, despite sharing a distinctive late-Avar culture. We reconstructed six-generation pedigrees at both sites including up to 450 closely related individuals, allowing per-generation demographic profiling of the communities. Despite different ancestry, these pedigrees together with large networks of distant relatedness show absence of consanguinity, patrilineal pattern with female exogamy, multiple reproductive partnerships (for example, levirate) and direct correlation of biological connectivity with archaeological markers of social status. The generation-long genetic barrier was maintained by systematically choosing partners with similar ancestry from other sites in the Avar realm. Leobersdorf had more biological connections with the Avar heartlands than with Mödling, which is instead linked to another site from the Vienna Basin with European-like ancestry. Mobility between sites was mostly due to female exogamy pointing to different marriage networks as the main driver of the maintenance of the genetic barrier.
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http://dx.doi.org/10.1038/s41586-024-08418-5 | DOI Listing |
medRxiv
July 2025
Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA.
Opioid analgesics are commonly prescribed to manage acute postoperative pain. However, individuals vary in their opioid dosing needs, with no validated biomarkers to guide prescribing. We used electronic health records data from the Million Veteran Program sample to investigate individual differences in opioid analgesic dosing following knee (n=18,540) or hip (n=9,363) arthroplasty in a predominantly male (93%) veteran sample.
View Article and Find Full Text PDFmedRxiv
June 2025
Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.
Background: The clinical utility of polygenic scores (PGS) is known to vary when training and test samples differ in ancestry, with recent work suggesting that sociodemographic differences can also impact PGS performance. However, the impact of belonging to multiple intersecting contexts on genetic risk remains understudied.
Methods: We analyzed lifetime disease odds ratios (OR) and absolute risks (AR) in high-PGS individuals across 106 two-way intersections of sociodemographic factors (sex, age, alcohol intake, smoking, income, deprivation).
medRxiv
May 2025
Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
The World Health Organization (WHO) ranks depression as the number one non-fatal contributor to the global burden of disease. Previous work finds that early intervention prior to onset leads to preferred outcomes. To examine depression prior to onset, risks are assessed in relation to depressive prodromal behavior and brain biomarkers.
View Article and Find Full Text PDFDrug Alcohol Depend
August 2025
Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Mental Illness Research, Education, and Clinical Center, Crescenz VAMC, Philadelphia, PA 19104, USA. Electronic address:
Introduction: Reducing or stopping substance use can result in withdrawal symptoms in physically dependent individuals. Appropriate management of withdrawal symptoms may be critical to the safety of individuals with substance use disorders (SUDs) and could help prevent a return to substance use. Although childhood adversity and genetic factors contribute to the development of SUDs, their individual and joint effects on withdrawal symptoms and severity are less clear.
View Article and Find Full Text PDFAlcohol Clin Exp Res (Hoboken)
June 2025
Department of Medical Sciences, Frank H. Netter School of Medicine at Quinnipiac University, North Haven, Connecticut, USA.
Background: In two 12-week, randomized, placebo-controlled trials (RCTs) in individuals with alcohol use disorder (AUD), topiramate significantly reduced heavy drinking days (HDDs), and alcohol-related problems. In a secondary analysis of those findings, we examined four broad measures of genetic risk-polygenic scores (PGS)-of problematic alcohol use (PAU), drinks per week (DPW), and time to relapse to any drinking (TR) and heavy drinking (THR) as moderators of topiramate's effect on HDDs and alcohol-related problems.
Methods: We analyzed data from 285 individuals with AUD (65.