CLN - The Sample
Recent research describes a polygenic risk score (PGS) reliably associated with adulthood obesity and shows consistent and indicative patterns in early childhood (Nat Med 2025; doi: 10.1038/s41591-025-03827-z).
By 2035, more than half of the global population will be overweight or obese, according to previous research. Obesity often begins during childhood and persists into adulthood. Therefore, predictors available in early life, such as genetic variants, could be valuable. Meanwhile, PGSs that capture an individual’s inherited polygenic susceptibility to a trait or disease have shown promise in enhancing disease risk prediction and population screening.
The researchers derived ancestry-specific and multiancestry PGS for BMI and obesity by leveraging the data of more than 5.1 million people from the results of a study by the Genetic Investigation of ANthropometric Traits (GIANT) consortium and 23andMe. The research is the largest genome-wide association study meta-analyses for body BMI. The researchers then tested whether their new PGS was associated with obesity using datasets of the physical and genetic characteristics of more than 500,000 people, including BMI data tracked over time from the Avon Longitudinal Study of Parents and Children (ALSPAC), a world-leading birth cohort study.
The multiancestry score explained 17.6% of BMI variation among UK Biobank participants of European ancestry. For other populations, the multiancestry score accounting for BMI variation ranged from 16% in East Asian Americans to 2.2% in rural Ugandans. In the ALSPAC study, children with higher PGSs showed accelerated BMI gain from age 2.5 years to adolescence, with an earlier second rise in BMI. Adding the PGS to predictors available at birth nearly doubled explained variance for BMI from age 5 onward. Up to age 5, adding the PGS to early-life BMI improved prediction of BMI at age 18.
Higher PGSs were associated with greater adult weight gain. In intensive lifestyle intervention trials, individuals with higher PGSs lost a more modest amount of weight in the first year (0.55 kg per standard deviation) but were more likely to regain it.
Overall, these data show that PGSs have the potential to improve obesity prediction, particularly when implemented early in life, the researchers wrote.
A recent study raises concerns about the analytical performance of HbA1c point-of-care (POC) devices (Clin Chem 2025; doi: 10.1093/clinchem/hvaf059).
An estimated 537 million adults live with diabetes as its worldwide prevalence continues to rise. The World Health Organization and diabetes specialty societies recommend diagnosing and monitoring diabetes with HbA1c. But in low- and middle-income countries (LMICs), access to HbA1c testing often is limited, particularly in rural areas. The situation has driven interest in POC testing for HbA1c. However, POC devices’ analytical performance remains poorly understood.
To provide supporting evidence for HbA1c POC selection and improve LMICs’ diabetes diagnosis and management, the study’s researchers evaluated 19 HbA1c POC devices’ analytical performance to determine whether devices met certification criteria and had hemoglobin (Hb) variant interference.
The researchers verified manufacturers’ claims about accuracy, imprecision, and interference from Hb variants based on established guidance from the Clinical and Laboratory Standards Institute protocols EP-15-A3 and EP-9-A3, international quality targets, and four certified International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and National Glycohemoglobin Standardization Program (NGSP) Secondary Reference Measurement Procedures (SRMPs). They assessed all POC devices for performance against both IFCC and NGSP certification criteria.
Only the Afinion 2 and the Quo-Lab devices met both the IFCC criteria and NGSP criteria with all four SRMPs. Twenty-six percent of the devices met only IFCC criteria and 47% did not meet either IFCC or NGSP criteria, despite most of these devices having an IFCC or NGSP certificate at the time of the study. Three devices showed clear interference from Hb variants.
These findings raise questions about the need for further measures to ensure that certified devices can prove consistent performance at regular intervals, rather than at a single time point that is then considered valid for a year.
The researchers noted that their study occurred under optimal laboratory conditions, and device performance may be worse in intended clinical settings.
Given the potential benefits of comprehensive genomic profiling (CGP) testing for cancer patients — such as increased rates of targeted therapy without increased treatment-related costs — more CGP testing may improve outcomes, a recent study says (JAMA Netw Open 2025; doi:10.1001/jamanetworkopen.2025.19963).
Clinical guidelines recommend biomarker testing to identify cancer patients who are eligible for targeted therapy. Evidence suggests that biomarker testing rates are below those recommended in guidelines, a situation associated with worse clinical outcomes and overall survival.
To explore the change in rates of CGP testing over time and compare targeted therapy rates and healthcare costs during first-line therapy, the researchers aimed to identify patients with newly diagnosed advanced breast, colorectal, gastric, nonsmall cell lung (NSCL), ovarian, and pancreatic cancer receiving CGP, non-CGP testing, or no biomarker testing in a retrospective cohort study using deidentified data from the Optum Labs Data Warehouse. They identified 26,311 adult patients diagnosed with advanced cancer during a 4-year period from this claims database of longitudinal health information on commercial health plan and Medicare Advantage enrollees. The patients were covered by the plans 12 months before and 6 months after their first advanced cancer diagnosis.
Molecular testing rates were suboptimal. Researchers saw evidence of molecular testing for only 35% of patients. However, testing rates increased across time for most cancer types from 32% in 2018 to 39% in 2021−2022. Patients with NSCL cancer and colorectal cancer with CGP testing were more likely to receive targeted therapy compared with patients who received non-CGP testing, with odds ratios of 1.57 and 2.34 respectively. Costs among patients with CGP showed no statistical difference from those with non-CGP testing for all the cancer types studied.
The authors noted that the study was limited by use of administrative claims, which can be subject to selection bias and do not include biomarker testing results or an algorithm for the testing categories based on procedure codes. As a result, these claims may potentially mischaracterize testing types.
Read the full September-October issue of CLN here.