An international team of scientists has sequenced Ludwig van Beethoven's genome for the first time using five genetically matching locks of the celebrated composer's hair.
The research, led by the University of Cambridge in the UK and colleagues, uncovers important information about the German composer's health and poses new questions about his recent ancestry and cause of death.
In total, the team conducted authentication tests on eight hair samples acquired from public and private collections in the UK, continental Europe and the US.
The study, published in the journal Current Biology, shows that DNA from five locks of hairall dating from the last seven years of Beethoven's lifeoriginate from a single individual matching the composer's documented ancestry.
By combining genetic data with closely examined provenance histories, researchers conclude these five locks are "almost certainly authentic."
The study's primary aim was to shed light on Beethoven's health problems, which famously include progressive hearing loss, beginning in his mid- to late-20s and eventually leading to him being functionally deaf by 1818.
The team also investigated possible genetic causes of Beethoven's chronic gastrointestinal complaints, and a severe liver disease that culminated in his death in 1827.
Beginning in his years in Bonn, Germany, the composer suffered from "wretched" gastrointestinal problems, which continued and worsened in Vienna, Austria.
In the summer of 1821, Beethoven had the first of at least two attacks of jaundice, a symptom of liver disease. Cirrhosis has long been viewed as the most likely cause of his death at age 56.
The researchers were unable to find a definitive cause for Beethoven's deafness or gastrointestinal problems. However, they did discover a number of significant genetic risk factors for liver disease.
They also found evidence of an infection with hepatitis B virus in the months before the composer's final illness.
"We can surmise from Beethoven's 'conversation books,' which he used during the last decade of his life, that his alcohol consumption was very regular, although it is difficult to estimate the volumes being consumed," said study lead author, Tristan Begg, from the University of Cambridge.
"While most of his contemporaries claim his consumption was moderate by early 19th century Viennese standards, there is not complete agreement among these sources, and this still likely amounted to quantities of alcohol known today to be harmful to the liver," Begg said.
If Beethovan's alcohol consumption was sufficiently heavy over a long enough period of time, the interaction with his genetic risk factors presents one possible explanation for his cirrhosis, the researchers said.
The team also suggests that Beethoven's hepatitis B infection might have driven the composer's severe liver disease, exacerbated by his alcohol intake and genetic risk. Beethoven's hearing loss has been linked to several potential causes, among them diseases with various degrees of genetic contributions.
Investigation of the authenticated hair samples did not reveal a simple genetic origin of the hearing loss, the researchers said.
"We cannot say definitely what killed Beethoven, but we can now at least confirm the presence of significant heritable risk, and an infection with hepatitis B virus," said Johannes Krause, from the Max Planck Institute of Evolutionary Anthropology.
"We can also eliminate several other less plausible genetic causes," Krause said. The team also analysed the genetics of his living relatives in Belgium but could not find matches among either of them.
Some of them share a paternal ancestor with Beethoven in the late 1500s and early 1600s based on genealogical studies, but they did not match the Y-Chromosome found in the authentic hair samples.
The team concluded that this was likely to be the result of at least one "extra-pair paternity event"a child resulting from an extramarital relationshipin Beethoven's direct paternal line.
