Genomic analyses of hair from Ludwig van Beethoven

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.