12 research outputs found
Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe
Rating Network Paths for Locality-Aware Overlay Construction and Routing
This paper investigates the rating of network paths,
i.e. acquiring quantized measures of path properties such as
round-trip time and available bandwidth. Comparing to finegrained
measurements, coarse-grained ratings are appealing in
that they are not only informative but also cheap to obtain.
Motivated by this insight, we firstly address the scalable
acquisition of path ratings by statistical inference. By observing
similarities to recommender systems, we examine the applicability
of solutions to recommender system and show that our
inference problem can be solved by a class of matrix factorization
techniques. A technical contribution is an active and progressive
inference framework that not only improves the accuracy by
selectively measuring more informative paths but also speeds
up the convergence for available bandwidth by incorporating its
measurement methodology.
Then, we investigate the usability of rating-based network
measurement and inference in applications. A case study is
performed on whether locality awareness can be achieved for
overlay networks of Pastry and BitTorrent using inferred ratings.
We show that such coarse-grained knowledge can improve the
performance of peer selection and that finer granularities do not
always lead to larger improvements
Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution
Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution
Genome-wide physical activity interactions in adiposity:a meta-analysis of 200,452 adults
Abstract
Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery
Genes of biological interest within 500 kb of lead SNPs associated with WC<sub>adjBMI</sub> or WHR<sub>adjBMI</sub>.
<p>Genes of biological interest within 500 kb of lead SNPs associated with WC<sub>adjBMI</sub> or WHR<sub>adjBMI</sub>.</p
Novel loci achieving genome-wide significance (P<5x10<sup>-8</sup>) in meta-analyses for PA-adjusted SNP main effect (P<sub>adjPA</sub>) or the joint test of SNP main effect and SNP-PA interaction (P<sub>joint</sub>).
<p>Novel loci achieving genome-wide significance (P<5x10<sup>-8</sup>) in meta-analyses for PA-adjusted SNP main effect (P<sub>adjPA</sub>) or the joint test of SNP main effect and SNP-PA interaction (P<sub>joint</sub>).</p