Researchers using phenome-wide association studies found that men with systemic lupus erythematosus were at increased risk for atrial fibrillation compared with women, according to findings published in Arthritis Care and Research.
“This is the first study to use phenome-wide association studies (PheWAS) to perform discovery research in SLE using the electronic health record,” April Barnado, MD, MSCI, of the Vanderbilt University Medical Center, told Healio Rheumatology. “PheWAS is a method that scans across billing codes in the EHR. It has replicated hundreds of known phenotype genotype associations and uncovered novel genetic associations in multiple autoimmune diseases. It is a cost-effective discovery tool that repurposes clinical EHR data for research.”
To determine whether PheWAS could be used as an EHR discovery tool for SLE, and whether it could discover new associations among men and women, the researchers drew data from a de-identified version of the Vanderbilt University Medical Center EHR, which includes more than 2.8 million patients. The researchers included 1,097 patients with SLE, who were matched by age, sex and race to 5,735 non-SLE control patients, in their study.
Researchers using phenome-wide association studies found that men with SLE were at increased risk for atrial fibrillation compared with women, according to researchers.
The researchers conducted PheWAS to compare SLE patients to their matched controls, as well as male to female patients. To control for multiple testing, Barnado and colleagues used a false discovery rate of 0.05.
According to the researchers, when focusing only on SLE patients and adjusting for age and race, men were more likely than women to have atrial fibrillation (OR = 4.5; FDR P = 3.23 x 10-3). A chart review confirmed cases of atrial fibrillation, with the majority of patients developing the condition following a diagnosis of SLE and demonstrating multiple risk factors. SLE was significantly association with atrial fibrillation among men even after adjusting for age, sex, race and coronary artery disease.
“In this proof-of-concept study, we demonstrate that PheWAS could identify SLE disease manifestations in the EHR validating PheWAS as a discovery tool,” Barnado said. “Using PheWAS to compare males and females with SLE, we report the first association of increased atrial fibrillation in males with SLE.”
According to Barnado, although SLE is more common in women, men may have a more accelerated disease course with increased disease damage and higher mortality. In addition, studies are limited with low numbers of male SLE subjects and often important comorbidities such as cardiovascular disease are not fully examined, she said.
“While an increased risk of coronary artery disease in SLE compared to the general population has been reported, the increased risk of [atrial fibrillation] has not been previously reported,” Barnado said. “This study highlights that males with SLE may be a particularly vulnerable patient group with increased risk of both coronary artery disease and [atrial fibrillation].”
She noted that, “recognizing this increased risk of [atrial fibrillation] could potentially lead to more expedited referrals and earlier diagnosis. As [atrial fibrillation] is associated with increased risk of stroke, heart failure and death, earlier diagnosis and treatment of [atrial fibrillation] is particularly important and may prevent these complications.” – by Jason Laday
Disclosure: The researchers report grant funding from the NIH.