Publication Date

4-24-2023

Document Type

Article

Publication Title

Current Biology

Volume

33

Issue

8

DOI

10.1016/j.cub.2023.02.041

First Page

1431

Last Page

1447.e22

Abstract

Ludwig van Beethoven (1770–1827) remains among the most influential and popular classical music composers. Health problems significantly impacted his career as a composer and pianist, including progressive hearing loss, recurring gastrointestinal complaints, and liver disease. In 1802, Beethoven requested that following his death, his disease be described and made public. Medical biographers have since proposed numerous hypotheses, including many substantially heritable conditions. Here we attempt a genomic analysis of Beethoven in order to elucidate potential underlying genetic and infectious causes of his illnesses. We incorporated improvements in ancient DNA methods into existing protocols for ancient hair samples, enabling the sequencing of high-coverage genomes from small quantities of historical hair. We analyzed eight independently sourced locks of hair attributed to Beethoven, five of which originated from a single European male. We deemed these matching samples to be almost certainly authentic and sequenced Beethoven's genome to 24-fold genomic coverage. Although we could not identify a genetic explanation for Beethoven's hearing disorder or gastrointestinal problems, we found that Beethoven had a genetic predisposition for liver disease. Metagenomic analyses revealed furthermore that Beethoven had a hepatitis B infection during at least the months prior to his death. Together with the genetic predisposition and his broadly accepted alcohol consumption, these present plausible explanations for Beethoven's severe liver disease, which culminated in his death. Unexpectedly, an analysis of Y chromosomes sequenced from five living members of the Van Beethoven patrilineage revealed the occurrence of an extra-pair paternity event in Ludwig van Beethoven's patrilineal ancestry.

Funding Number

REFORM/SC2020/029

Funding Sponsor

European Commission

Keywords

ancient DNA, extra-pair paternity, genetic genealogy, genobiography, geo-genetic triangulation, hair, hepatitis B virus, Ludwig van Beethoven, medical genetics, the Beethoven genome project

Comments

Full author list: Tristan James Alexander Begg, Axel Schmidt, Arthur Kocher, Maarten H.D. Larmuseau, Göran Runfeldt, Paul Andrew Maier, John D. Wilson, Rodrigo Barquera, Carlo Maj, András Szolek, Michael Sager, Stephen Clayton, Alexander Peltzer, Ruoyun Hui, Julia Ronge, Ella Reiter, Cäcilia Freund, Marta Burri, Franziska Aron, Anthi Tiliakou, Joanna Osborn, Doron M. Behar, Malte Boecker, Guido Brandt, Isabelle Cleynen, Christian Strassburg, Kay Prüfer, Denise Kühnert, William Rhea Meredith, Markus M. Nöthen, Robert David Attenborough, Toomas Kivisild, Johannes Krause

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Department

Music and Dance

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