UK Biobank

Posted on Obesity, Pain Management

Abdominal fat linked to chronic pain, especially in women

Reducing this fat may reduce chronic pain particularly if it’s at multiple body sites
“Reducing this fat may help reduce chronic pain, especially if it is present in multiple body sites.”

Reducing excess fat deposits in the abdomen may help reduce chronic musculoskeletal pain, especially if it’s experienced at multiple body sites, suggest the researchers. Previously published research has shown that obesity is associated with musculoskeletal pain. Still, it’s not known if excess fat tissue is linked to chronic musculoskeletal pain at multiple body sites, say the researchers. To find out, they drew on data from 32,409 participants in the UK Biobank study who completed questionnaires and underwent health assessments. Around half (51%) were women, and their average age was 55.

They underwent MRI scans of their abdomen to measure the amount of fat around the abdominal organs (visceral adipose tissue or VAT)  and the amount of fat just under the skin that can be pinched (subcutaneous adipose tissue or SAT).  When attending for their scan, participants were asked if they had experienced any pain in their neck/shoulder, back, hip, knee or ’all over the body’ for more than 3 months.  The MRI scan and pain assessments were repeated around 2 years later for 638 participants. Comprehensive analyses showed a dose-response association between the number of chronic pain sites and VAT, SAT, the ratio of the two, and weight (BMI).  The association was stronger in women, among whom the odds ratio of a higher number of chronic pain sites was twice as high for VAT and 60% greater for both SAT and the VAT: SAT ratio. In men, these odds ratios were 34% 39%, and 13% higher, respectively. 

Higher levels of fat tissue were also associated with greater odds of reporting chronic pain, and again the association was more pronounced in women.  All these associations remained even after adjusting for age, height, ethnicity, household income, educational attainment, alcohol intake, smoking status, physical activity, coexisting conditions, sleep duration, psychological problems and length of follow-up.

This is an observational study, and as such, can’t establish cause and effect, and the authors also acknowledge various limitations. These include the relatively small size of the repeat imaging sample and the absence of an assessment of severity in the pain questionnaire. They add that more follow-up visits would also have allowed more information to be gathered on patterns and fluctuations in the number of chronic pain sites. However, they conclude: “Abdominal adipose tissue was associated with chronic musculoskeletal pain, suggesting that excessive and ectopic fat depositions may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain.  Therefore, reducing abdominal adiposity may be considered a target for chronic pain management, particularly in those with pain in multiple sites and widespread pain.” They suggest that the stronger associations seen in women may be a consequence of sex differences in fat distribution and hormones.

Posted on Gastrointestinal disorders

Multi-population risk scores could improve risk prediction for inflammatory bowel diseases, study finds

Using genetic data from nearly 30,000 people, Mount Sinai researchers have built risk scores from a combination of datasets representing distinct ancestral populations that improve prediction of risk for inflammatory bowel diseases (IBD) including Crohn’s disease and ulcerative colitis. The study was published in Gastroenterology on December 24.

The researchers found that polygenic risk scores, built using association data from multiple populations in Mount Sinai’s multi-ethnic BioMe Biobank, maximized IBD predictions for every population in the biobank. BioMe is a system-wide effort at Mount Sinai that is revolutionizing diagnosis and classification of diseases according to the patient’s molecular profile. The study showed that risk scores calculated from integrating data significantly improved predictions among individuals with European, Ashkenazi Jewish, and Hispanic ancestry in BioMe, as well as European individuals in the UK Biobank, which contains biological and medical data on half a million people between ages 40 and 69 living in the UK. Predictive power was lower for patients with African ancestry, likely due to substantially smaller reference datasets and substantially greater genetic diversity within populations of African descent.

“The ability to accurately predict genetic disease risk in individuals across ancestries is a critical avenue that may positively affect patient outcomes, as early interventions and even preventive measures are being considered and developed,” says the study’s senior author Judy H. Cho, MD, Dean of Translational Genetics and Director of The Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai. “These findings support a need for greater genetic diversity, including more data on African American populations, to enhance disease risk predictions and reduce health disparities for all populations.”

These polygenic risk scores–representing an estimate of overall risk based on the sum of an individual’s many, mostly common, genetic variants–were calculated using IBD association data from cohorts with European, African American, and Ashkenazi Jewish backgrounds. Additionally, researchers assessed rare variants in genes associated with very-early-onset IBD within each population and found that African American carriers of uncommon LRBA variants showed reduced expression of both proteins LRBA and CTLA-4. LRBA deficiency increases susceptibility to IBD and results in lower CTLA-4 expression, which can be reversed with the commonly prescribed antimalarial drug chloroquine. Future studies by the Cho Laboratory will focus on predicting which subsets of patients might benefit from targeting this pathway.

“Since lowered LRBA and CTLA-4 expression can lead to IBD, it’s encouraging that chloroquine is able to partially recover expression,” says the study’s first author Kyle Gettler, PhD, postdoctoral fellow in the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai.