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medRxiv PreprintsInternational11 October 2026

Genetic Variant Burden Rises with BMI: Insights from Rare and Low-Frequency Variants in Obesity

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Adult obesity, including morbid obesity, has reached epidemic proportions worldwide. Yet, the current genetic models based on BMI-associated common variants identified through genome-wide association studies (GWAS) explain only a modest fraction of BMI variability. Contribution of rare and low-frequency variants to polygenic obesity remains incompletely defined. Leveraging whole-exome sequences of 1138 adults spanning normal-weight, overweight, obese and morbidly obese (MO) categories from Kuwait and Qatar, we catalogued cohort-specific rare and low-frequency deleterious variants differentiati
— medRxiv Preprints
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