US study uncovers 275 million entirely new genetic variants

FILE PHOTO: A DNA double helix is seen in an undated artist’s illustration released by the National Human Genome Research Institute to Reuters on May 15, 2012. REUTERS/National Human Genome Research Institute/Handout/File Photo

A study that analyzed the genetic code of a quarter of a million U.S. volunteers found more than 275 million entirely new variants that may help explain why some groups are more prone to disease than others, researchers reported on Monday.

The whole genome sequencing data from a wide range of Americans aims to address the historical lack of diversity in existing genomic datasets by focusing on previously under-represented groups. The U.S. National Institutes of Health-funded “All of Us” study turned up 1 billion genetic variants in total.

“Sequencing diverse populations can lead to new drug targets that are relevant to everyone,” said Dr. Josh Denny, a study author and its chief executive. “It can also help uncover disparities that lead to specific treatments for people that are experiencing higher burdens of disease or different disease.”

Although many genetic variants have no impact on health, nearly 4 million of the newly discovered differences in the genetic code are located in areas that may be tied to disease risk, the researchers reported in a series of papers published in Nature and related journals.

“This is huge,” said Denny. The study aims to eventually collect DNA and other health data on 1 million people in hopes of better understanding genetic influences on health and disease.

Nearly 90% of genomic studies to date have been done in people of European ancestry, which has led to a narrow understanding of the biology of diseases and slowed the development of drugs and prevention strategies effective in diverse populations, the leaders of several NIH departments wrote in a related commentary.

“It’s a huge gap, obviously, because most of the world’s population is not of European ancestry,” Denny said.

Recent studies have already shown how genetic diversity can impact disease risk. Variants in the APOL1 gene discovered in 2010 help account for 70% of the increased risk for chronic kidney disease and dialysis seen in people in the U.S. with sub-Saharan African ancestry.

Likewise, a class of drugs called PCSK9 inhibitors that dramatically lower very high levels of low-density lipoprotein (LDL) – the so-called bad cholesterol – were discovered by sequencing the genetic code of 5,000 people in Dallas of African ancestry.

Much more work is needed to understand how the new trove of genetic variants contributes to various health conditions, but the scientists believe they could be used to refine tools used to calculate a person’s risk for disease.