Low-frequency coding variants associated with body-mass-index impact the success of bariatric surgery

Context A recent study identified 14 low-frequency coding variants associated with body-mass-index (BMI) in 718,734 individuals predominantly of European ancestry. Objective and design The 14 low-frequency coding variants were genotyped or sequenced in 342 French adults with severe/morbid obesity and 574 French adult controls from the general population. We built risk and protective genetic scores (GS) based on 6 BMI-increasing and 5 BMI-decreasing low-frequency coding variants that were polymorphic in our study. We investigated the association of the two GS with i) the risk of severe/morbid obesity, ii) BMI variation before weight-loss intervention, iii) BMI change in response to an 18-month lifestyle/behavioral intervention program, and iv) BMI change up to 24 months after bariatric surgery. Results While the risk GS was not associated with severe/morbid obesity status, BMI-decreasing low-frequency coding variants were significantly less frequent in patients with severe/morbid obesity than in French adults from the general population. Neither the risk nor the protective GS was associated with BMI before intervention in patients with severe/morbid obesity, nor did they impact BMI change in response to a lifestyle/behavioral modification program. The protective GS was associated with a greater BMI decrease following bariatric surgery. The risk and protective GS were associated with a higher and lower risk of BMI regain after bariatric surgery. Conclusion Our data indicate that in populations of European descent, low-frequency coding variants associated with BMI in the general population also impact the outcomes of bariatric surgery in patients with severe/morbid obesity.

Multi-trait association studies discover pleiotropic loci between Alzheimer’s disease and cardiometabolic traits

Background Identification of genetic risk factors that are shared between Alzheimer’s disease (AD) and other traits, i.e., pleiotropy, can help improve our understanding of the etiology of AD and potentially detect new therapeutic targets. Previous epidemiological correlations observed between cardiometabolic traits and AD led us to assess the pleiotropy between these traits. Methods We performed a set of bivariate genome-wide association studies coupled with colocalization analysis to identify loci that are shared between AD and eleven cardiometabolic traits. For each of these loci, we performed colocalization with Genotype-Tissue Expression (GTEx) project expression quantitative trait loci (eQTL) to identify candidate causal genes. Results We identified three previously unreported pleiotropic trait associations at known AD loci as well as four novel pleiotropic loci. One associated locus was tagged by a low-frequency coding variant in the gene DOCK4 and is potentially implicated in its alternative splicing. Colocalization with GTEx eQTL data identified additional candidate genes for the loci we detected, including ACE, the target of the hypertensive drug class of ACE inhibitors. We found that the allele associated with decreased ACE expression in brain tissue was also associated with increased risk of AD, providing human genetic evidence of a potential increase in AD risk from use of an established anti-hypertensive therapeutic. Conclusion Our results support a complex genetic relationship between AD and these cardiometabolic traits, and the candidate causal genes identified suggest that blood pressure and immune response play a role in the pleiotropy between these traits.

Soliton orthogonal frequency division multiplexing with phase–frequency coding on the base of inverse scattering transform

We propose a method for increasing the speed and spectral efficiency of information transmission over soliton communication lines, based on algorithms for solving inverse and direct scattering problems, in the frame of a modern soliton orthogonal frequency division multiplexing (SOFDM) approach. The proposed method uses a simultaneous phase and frequency coding. This phase–frequency coding method retains all the technological advantages of the SOFDM method, and due to the additional frequency coding, a noticeable increase in the information transfer rate over the soliton optical lines is expected. Numerical modeling confirmed the proposed method for telecommunication applications’ prospects.