RESUMO
BACKGROUND: Bariatric surgery (BS) is currently the most effective long-term treatment of severe obesity. However, the interindividual variability observed in surgical outcomes suggests a moderating effect of several factors, including individual genetic background. This study aimed to investigate the contribution of the genetic architecture of body mass index (BMI) to the variability in weight loss outcomes after BS. METHODS: A total of 106 patients with severe obesity who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy were followed up for 5 years. Changes in BMI (BMIchange) and percentage of total weight loss (%TWL) were evaluated during the postoperative period. Polygenic risk scores (PRSs), including 50 genetic variants, were calculated for each participant to determine their genetic risk of high BMI based on a previous genome-wide association study. Generalized estimating equation models were used to study the role of the individual's polygenic score and other factors on BMIchange and %TWL in the long term after surgery. RESULTS: This study found an effect of the polygenic score on %TWL and BMIchange, in which patients with lower scores had better outcomes after surgery than those with higher scores. Furthermore, when analyzing only patients who underwent RYGB, the results were replicated, showing greater weight loss after surgery for patients with lower polygenic scores. DISCUSSION: Our results indicate that genetic background assessed with PRSs, along with other individual factors, such as biological sex, age, and preoperative BMI, has an effect on BS outcomes and could represent a useful tool for estimating surgical outcomes in advance.
RESUMO
BACKGROUND: Obesity is a polygenic multifactorial disease. Recent genome-wide association studies have identified several common loci associated with obesity-related phenotypes. Bariatric surgery (BS) is the most effective long-term treatment for patients with severe obesity. The huge variability in BS outcomes between patients suggests a moderating effect of several factors, including the genetic architecture of the patients. OBJECTIVE: To examine the role of a genetic risk score (GRS) based on 7 polymorphisms in 5 obesity-candidate genes (FTO, MC4R, SIRT1, LEP, and LEPR) on weight loss after BS. SETTING: University hospital in Spain. METHODS: We evaluated a cohort of 104 patients with severe obesity submitted to BS (Roux-en-Y gastric bypass or sleeve gastrectomy) followed up for >60 months (lost to follow-up, 19.23%). A GRS was calculated for each patient, considering the number of carried risk alleles for the analyzed genes. During the postoperative period, the percentage of excess weight loss total weight loss and changes in body mass index were evaluated. Generalized estimating equation models were used for the prospective analysis of the variation of these variables in relation to the GRS. RESULTS: The longitudinal model showed a significant effect of the GRS on the percentage of excess weight loss (P = 1.5 × 10-5), percentage of total weight loss (P = 3.1 × 10-8), and change in body mass index (P = 7.8 × 10-16) over time. Individuals with a low GRS seemed to experience better outcomes at 24 and 60 months after surgery than those with a higher GRS. CONCLUSION: The use of the GRS in considering the polygenic nature of obesity seems to be a useful tool to better understand the outcome of patients with obesity after BS.
RESUMO
Schizophrenia (SZ) is a complex disorder with a highly polygenic inheritance. It can be conceived as the extreme expression of a continuum of traits that are present in the general population often broadly referred to as schizotypy. However, it is still poorly understood how these traits overlap genetically with the disorder. We investigated whether polygenic risk for SZ is associated with these disorder-related phenotypes (schizotypy, psychotic-like experiences, and subclinical psychopathology) in a sample of 253 non-clinically identified participants. Polygenic risk scores (PRSs) were constructed based on the latest SZ genome-wide association study using the PRS-CS method. Their association with self-report and interview measures of SZ-related traits was tested. No association with either schizotypy or psychotic-like experiences was found. However, we identified a significant association with the Motor Change subscale of the Comprehensive Assessment of At-Risk Mental States (CAARMS) interview. Our results indicate that the genetic overlap of SZ with schizotypy and psychotic-like experiences is less robust than previously hypothesized. The relationship between high PRS for SZ and motor abnormalities could reflect neurodevelopmental processes associated with psychosis proneness and SZ.
