Research: New insights into genetic causes of high cholesterol

According to new research led by geneticists at the University of Pittsburgh School of Public Health in collaboration with several other organisations, including the University of Otago and the Samoan health research community, the discovery of a genetic variant that is relatively common among people of Polynesian ancestry, but incredibly rare in most other populations, is providing hints to the genetic underpinnings of high cholesterol in all people.
The unexpected result underscores the value of ensuring diversity in genetic databases and was just published this week in the journal Human Genetics and Genomics Advances.
“If we had only been looking in populations with European ancestry, we might have missed this finding entirely,” said lead author Jenna Carlson, PhD, assistant professor of human genetics and biostatistics at Pitt Public Health. “It was through the generosity of thousands of Polynesian people that we were able to find this variant, which is a smoking gun that will spark new research into the biology underlying cholesterol.”

According to the World Health Organization, high cholesterol is a leading contributor to disease burden in nations of all income levels, is a risk factor for heart disease and stroke, and is thought to be responsible for 2.6 million deaths annually globally.
In order to investigate a signal that surfaced in a comprehensive genome-wide search for genes linked to lipids or fats, in the body, Carlson and her team built their study. It was suggested that a chromosome 5 gene variant might be connected to cholesterol. Using genetic information from 2,851 Samoan adults from the Obesity, Lifestyle, and Genetic Adaptations (OLAGA) Study Group who had also provided health information, including lipid panels, the team set out to “fine map” the area. The association between the variant and cholesterol was found in 3,276 additional Polynesian individuals from Samoa, American Samoa, and Aotearoa New Zealand. This was done to confirm the initial finding.
“We don’t know a lot about this variant because it’s not seen in published genome references, which overrepresent European ancestry individuals – it’s virtually nonexistent in European ancestry populations, has a very low frequency in South Asians and isn’t even particularly common in eastern Polynesian people, such as Maori living in Aotearoa New Zealand,” Carlson said. “But the way it’s linked to lipid panels in Samoan people tells us that this gene is important to cholesterol, something we didn’t know before. By further exploring BTNL9, we might someday discover new ways to help everyone maintain healthy cholesterol levels.”