Polygenic risk score identifies more patients with AAA than current guidelines
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Researchers identified 14 novel genetic associations for abdominal aortic aneurysm that when added to a polygenic risk score may find more patients at increased risk for the condition.
“This study has doubled the number of genetic associations with abdominal aortic aneurysm, adding greatly to our understanding of the disease mechanisms,” Philip S. Tsao, PhD, professor of cardiovascular medicine at Stanford University School of Medicine and director of the VA Palo Alto Epidemiology Research and Information Center for Genomics in California, said in a press release. “This new information can enhance screening protocols and help identify individuals at risk for abdominal aortic aneurysm.”
Data from Million Veteran Program
In this genome-wide association study published in Circulation, Derek Klarin, MD, vascular surgery fellow at University of Florida College of Medicine in Gainesville, and colleagues tested approximately 18 million DNA sequence variants with AAA in participants from the Million Veteran Program. These were tested in 7,642 patients with AAA (mean age, 76 years; 99% men) and 172,172 controls (mean age, 67 years; 92% men), with independent replication in 4,972 patients with AAA and 99,858 controls.
Researchers used Mendelian randomization to assess causal effects of BP on AAA. In addition, the relationship between AAA risk and aneurysm variants were analyzed in the cerebral, lower extremity and iliac arterial beds. A genome-wide polygenic risk score was also derived to identify patients who were at greater risk for AAA.
Researchers identified 14 novel loci, which updated the total of known significant AAA loci to 24.
Through Mendelian randomization, a genetic increase of 10 mm Hg in diastolic BP was linked to an increased risk for AAA (OR per 10 mm Hg increase = 1.43; 95% CI, 1.24-1.66; P = 1.6 x 10-6). This was not observed in genetic increases of 10 mm Hg in systolic BP (OR per 10 mm Hg increase = 1.06; 95% CI, 0.97-1.15; P = .2).
Nineteen of 24 variants for AAA risk were linked to aneurysms in at least one other vascular territory.
The polygenic risk score, which included 29 variants, was strongly linked to AAA (OR = 1.26; 95% CI, 1.18-1.36; P per standard deviation increase in polygenic risk score = 2.7 x 10-11). This association was independent of smoking risk factors and family history (OR = 1.24; 95% CI, 1.14-1.35; P per standard deviation increase in polygenic risk score = 1.27 x 10-6). The polygenic risk score was able to identify a greater subset of patients with AAA compared with screening trials that informed current guidelines.
Effects of polygenic risk scores
“Results from our study suggest that [polygenic risk scores] represent an orthogonal source of disease risk not captured by standard AAA risk factors, and testing individuals with a high AAA [polygenic risk score] through a noninvasive, abdominal duplex study may increase the yield of AAA screening,” Klarin and colleagues wrote.
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