Is RA In Your Genes? Study Identifies Predictive Family Comorbidities

A study published in Arthritis Care & Research analyzed the correlation between 79 different family comorbidities and rheumatoid arthritis (RA).

“Family history of rheumatoid arthritis (RA) is known to be an important predictor of RA, even after accounting for genetic and environmental factors,” the researchers observed, adding, “It is plausible that family history of other comorbidities might also predispose to RA due to overlapping heritability or disease mechanisms, helping to identify those at higher risk for RA.”

Although previous studies found correlations between RA and a family history of conditions such as type 1 diabetes and thyroid disease, they did not control for confounding factors such as smoking status, and they did not consider non-autoimmune comorbidities.

To that end, the researchers conducted a case-control study that encompassed 821 RA cases in the Mayo Clinic Biobank. RA cases were age-, sex-, recruitment year-, and location-matched 1:3 to controls. Patients self-reported family history and adjusters. The authors calculated logistic regression estimated odds ratios (ORs) and CIs for RA risk using the presence of family history for each comorbidity and adjusted for factors including body mass index (BMI), race, and smoking.

Patients reported family history of comorbidities including RA; autoimmune diseases such as rheumatologic autoimmune disorder, Crohn’s disease or ulcerative colitis, celiac disease, and hyperthyroidism/hypothyroidism; 22 cancers, including thyroid, lung, breast, esophageal, pancreatic, stomach, colon or rectal, liver, uterine/endometrial, cervical, ovarian, prostate, testicular, bone, kidney, urinary/bladder, melanoma, nonmelanoma skin cancer, sarcoma, leukemia, lymphoma, and other cancer; and non-autoimmune diseases such as osteoarthritis (OA) and obstructive sleep apnea (OSA). Patients responded to the question, “Do or did any of your first-degree relatives (parents, sisters, brothers, children) have this condition?” by answering “yes,” “no,” or “don’t know”; during primary analysis, a “don’t know” response was considered a “no.” Missing data for each comorbidity ranged from 7% to 13%.

The authors observed a correlation between RA and family history of several comorbidities, including rheumatologic autoimmune diseases (adjusted OR [aOR] 1.89, 95% CI 1.41-2.52), pulmonary fibrosis (aOR 2.12, 95% CI 1.16-3.80), inflammatory bowel disease (aOR 1.45, 95% CI 1.05-1.98), hyper/hypothyroidism (aOR 1.34, 95% CI 1.10,1.63), and obstructive sleep apnea (aOR 1.28, 95% CI 1.05-1.55). A statistically decreased risk was observed in patients with a family history of Parkinson’s disease (aOR 0.70, 95% CI 0.49-0.98) and type 2 diabetes (aOR 0.81, 95% CI 0.67-0.97), although this did not achieve the pre-specified P < 0.01 significance threshold.

“Analyses among 143 cases of incident RA were similar and also suggested an association with family history of autism (OR 10.5, 95% CI 2.51,71.3),” the researchers added.

The study authors stated in sum that “self-reported family history of several comorbidities besides RA were associated with increased risk for RA, including other rheumatologic diseases such as lupus and scleroderma, autoimmune diseases such as thyroid disease and IBD, and potentially non-autoimmune conditions such as pulmonary fibrosis, OSA, and autism. These findings can help refine tools to predict RA risk.”