SEATTLE (GenomeWeb) – The Healthy Nevada Project, a large-scale population health genetic screening study, has identified several hundred individuals at risk of one of three inherited conditions so far, more than half of whom would have been missed by current screening guidelines, according to findings presented here at the American College of Medical Genetics and Genomics annual meeting yesterday. The hope is that by identifying these patients early, mortality and morbidity related to their genetic disease risk could be lowered.
The project started in 2016 with a pilot study involving 1,000 individuals and moved to a larger second phase a year ago that will enroll up to 250,000 Nevada residents of diverse backgrounds.
Participants are offered exome sequencing at no cost, which is conducted by the project's partner Helix. Those who agree receive pathogenic or likely pathogenic variant findings for so-called CDC Tier 1 conditions, which include hereditary breast and ovarian cancer (BRCA1 and BRCA2), familial hypercholesterolemia, and Lynch syndrome. Yesterday, the project announced a partnership with Genome Medical to provide genetic counseling and education services for the project.
The study started returning results last September, which came with an education program about inherited diseases for both participants and physicians.
In a presentation at ACMG yesterday, Joseph Grzymski, co-director of the Renown Institute for Health Innovation and a leader of the Healthy Nevada Project, said that as of January the project had returned positive results for 290 of 23,500 participants whose exomes they had analyzed, or 1.23 percent. This number is slightly higher than what would be expected in a general population but has not been corrected to account for individuals from the same family, he said.
A total of 129 (1 in 183 people) received a positive result for hereditary breast or ovarian cancer (HBOC) risk; 115 (1 in 205) a familial hypercholesterolemia (FH) risk result; and 46 (1 in 500) a Lynch syndrome mutation.
The majority of those with a positive result had no family history of the disease, so were not already aware of their increased risk. The researchers queried 249 individuals with a positive result and found that 64 percent of those with a Lynch syndrome result, 63 percent of those with an FH result, and 56 percent of those with an HBOC result reported no known family history.
Grzymski said that these individuals would be missed by current screening guidelines for genetic testing that rely on family history. While some participants likely joined the study because they had a suspicion they might be at risk for something, for others, a positive result came "out of the blue", he said.
To see how the genetic screening results affect study participants' healthcare, and whether they were already affected by the disease they are genetically at risk for, the researchers took a look at the electronic health records of 243 individuals with a positive result. They found that just five months or less after receiving their study results, more than 15 percent already had clinical follow-up and a genetic diagnosis in their EHR.
Specifically, of 108 with a BRCA mutation (with a mean age of 50), 21 (with a mean age of 55) already had a diagnosis of breast, ovarian, or another type of cancer, and 11 had a genetic diagnosis prior to the project. Another 17 had their project test result added to their EHR.
For Lynch syndrome, of 37 with a positive result (with a mean age of 54), 15 (with a mean age of 46) already had a known malignancy, and three had a prior genetic diagnosis. Two participants had a genetic diagnosis added to their health record after obtaining the project result.
Of 98 people with a positive FH result (with a mean age of 49), 26 (with a mean age of 63) already had signs of atherosclerotic cardiovascular disease (ASCVD), and four had a prior genetic diagnosis. Another 18 had their genetic test results added to their EHR following the disclosure of the result.
Grzymski noted that because the mean age of those with a positive result was quite high in the study, a significant number of them were already diagnosed with the disease they were at risk for, suggesting that population screening should maybe target a younger population in order to catch those at risk before they develop disease.
The study will continue to enroll additional participants and to follow them longitudinally, he said.