Prevalence of genetic causes of obesity in clinical practice

Abstract

BackgroundWhile obesity is common in the United States, monogenic obesity is rare, accounting for approximately 5% of individuals with obesity. New targeted therapies for genetic forms of obesity are available but there is limited guidance on who requires testing. The aims of this study were to evaluate the prevalence of potentially clinically significant variants among individuals in Pediatric Endocrinology or Medical Weight Center clinics at a single center and to identify clinical characteristics that may make genetic obesity more likely.MethodsChildren and adults who had a genetic test for obesity, Uncovering Rare Obesity Gene panel, ordered during routine clinic visits from December 2019 to March 2021 were identified.ResultsOf the 139 patients with testing ordered, 117 had available results and clinical data. Over 40% (52/117, 44%) had at least one positive result (variant) with a variant that is considered pathogenic, likely pathogenic, or a variant of uncertain significance. No association was detected between age, sex, race, and body mass index (BMI) or BMI z‐score with a variant. Twenty‐six individuals (22%) had one or more variants in genes associated with Bardet Biedl Syndrome, and 8 (6.8%) of them had pathogenic variants, higher than expected.ConclusionOverall, clinical suspicion for genetic obesity is important in determining who requires genetic testing but no clinical factors were found to predict results. While obesity is multifactorial, novel medications for genetic forms of obesity indicate the need for evidence‐based guidelines for who requires genetic testing for obesity.

The Tip of the Iceberg: Genotype of Puerto Rican Pediatric Obesity

“…Among the children tested in our study, 73% had at least one variant reported, 61% had more than one variant, and 39% had one variant. Other studies showed similar frequencies, such as 61.5%, 69.4%, and 30.1% [26,29]. Also, variants in our study and the other studies were found equally among all age groups [26,29].…”

“…The genetic testing conducted in our study produced 1% positive results, 73% indeterminate results, and 27% negative results. In comparison to other studies, this finding is comparable [26,29]. Furthermore, the group of tests in similar studies exhibited a comparable distribution of favorable outcomes, despite 38.5% producing unfavorable results.…”

“…This study conducted a retrospective analysis of 103 pediatric patients, a sample size that appears to be sufficient in comparison to previous studies [26,29]. None of the subjects studied were siblings or had consanguinity among families; comparable studies did not investigate consanguinity or found that some subjects were related [26,27,29]. Our cohort had a BMI ≥ 97th percentile of roughly 99% and 84% hyperphagia, similarly seen in Roberts et al's [26].…”

“…Furthermore, the group of tests in similar studies exhibited a comparable distribution of favorable outcomes, despite 38.5% producing unfavorable results. The exact percentage of uncertain results was not explicitly stated [26,29]. The presence of indeterminate genetic results within our cohort underscores the necessity for additional research endeavors aimed at enhancing comprehension and establishing correlations between genetic variants associated with obesity and the clinical manifestations of genetic obesity.…”

“…To our knowledge, this is the first study in Puerto Rico that explores the genetics of obesity in children. This study conducted a retrospective analysis of 103 pediatric patients, a sample size that appears to be sufficient in comparison to previous studies [26,29]. None of the subjects studied were siblings or had consanguinity among families; comparable studies did not investigate consanguinity or found that some subjects were related [26,27,29].…”