This study is a non-drug, multicenter, prospective cohort study. It will be conducted in 300 volunteers from 12 to 45 years of age (inclusive) with a diagnosis of Down syndrome from 3 countries (France, Spain, United Kingdom (UK)). The basic hypotheses of the study are the following: 1. Diseases (and comorbidity) arise from one or more biological networks perturbed by the genetic disorder (trisomy 21) through interaction with environmental risks factors and epigenetic changes. 2. Health comorbidity patterns in DS individuals (particularly of obesity and related conditions) will likely vary by age and sex. 3. Obesity comorbidity patterns will relate to variation in factors including lifestyle, stress-response, severity of intellectual disability (ID) and variation in cognitive domains such as executive functioning. 4. Stress responses, as measured with cortisol concentrations, will differentiate individuals with DS who are obese and those who are not. Extremes in phenotype (Obese vs. Non-obese) will be related to differences in the metabolomic, transcriptomic, and microbiome concentrations.