scispace - formally typeset
Open AccessJournal ArticleDOI

Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose

Peitao Wu, +68 more
- 07 May 2020 - 
- Vol. 15, Iss: 5, pp 1-17
Reads0
Chats0
TLDR
The identification of loci exhibiting potential interaction with baseline smoking status provides evidence for genetic interactions with smoking exposure that may explain some of the heterogeneity in the association between smoking and T2D.
Abstract
Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. never) on incident T2D and fasting glucose (FG). Analyses were performed in participants of European (EA) and African ancestry (AA) separately. Discovery analyses were conducted using genotype data from the 50,000-single-nucleotide polymorphism (SNP) ITMAT-Broad-CARe (IBC) array in 5 cohorts from from the Candidate Gene Association Resource Consortium (n = 23,189). Replication was performed in up to 16 studies from the Cohorts for Heart Aging Research in Genomic Epidemiology Consortium (n = 74,584). In meta-analysis of discovery and replication estimates, 5 SNPs met at least one criterion for potential interaction with smoking on incident T2D at p<1x10-7 (adjusted for multiple hypothesis-testing with the IBC array). Two SNPs had significant joint effects in the overall model and significant main effects only in one smoking stratum: rs140637 (FBN1) in AA individuals had a significant main effect only among smokers, and rs1444261 (closest gene C2orf63) in EA individuals had a significant main effect only among nonsmokers. Three additional SNPs were identified as having potential interaction by exhibiting a significant main effects only in smokers: rs1801232 (CUBN) in AA individuals, rs12243326 (TCF7L2) in EA individuals, and rs4132670 (TCF7L2) in EA individuals. No SNP met significance for potential interaction with smoking on baseline FG. The identification of these loci provides evidence for genetic interactions with smoking exposure that may explain some of the heterogeneity in the association between smoking and T2D.

read more

Content maybe subject to copyright    Report

Citations
More filters

The genetic architecture of type 2 diabetes

Christian Fuchsberger, +300 more
TL;DR: Large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes, but most fell within regions previously identified by genome-wide association studies.

Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps

Anubha Mahajan, +113 more
Abstract: We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%, 14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.

Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

A. Mesut Erzurumluoglu, +174 more
TL;DR: In this article, a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants) was performed to investigate the association of SNVs with smoking behavior traits.
Journal ArticleDOI

The effect of corn straw return on corn production in Northeast China: An integrated regional evaluation with meta-analysis and system dynamics

TL;DR: Wang et al. as discussed by the authors studied the effects of corn straw return on corn yield increase with meta-analysis, and they concluded that the optimal amount of straw return is 48% of the corn straw, which brings 5.83% increase in corn yield.
Journal ArticleDOI

Tolerance of Listeria monocytogenes to biocides used in food processing environments.

TL;DR: In this article, the authors discuss the current literature on the ability of L monocytogenes strains to tolerate biocides especially quaternary ammonium compounds as well as the mechanisms of tolerance towards Biocides including the activation of efflux pump systems.
References
More filters
Journal ArticleDOI

The Genotype-Tissue Expression (GTEx) project

John T. Lonsdale, +129 more
- 29 May 2013 - 
TL;DR: The Genotype-Tissue Expression (GTEx) project is described, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.
Journal ArticleDOI

Annotation of functional variation in personal genomes using RegulomeDB

TL;DR: A novel approach and database, RegulomeDB, which guides interpretation of regulatory variants in the human genome, which includes high-throughput, experimental data sets from ENCODE and other sources, as well as computational predictions and manual annotations to identify putative regulatory potential and identify functional variants.
Related Papers (5)

Genome-wide meta-analyses identify multiple loci associated with smoking behavior

Helena Furberg, +123 more
- 01 May 2010 -