Dataset Information

No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.

ABSTRACT: Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2 × 10(-8). This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.

SUBMITTER: Baumert J

PROVIDER: S-EPMC4281156 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.

Baumert Jens J Huang Jie J McKnight Barbara B Sabater-Lleal Maria M Steri Maristella M Chu Audrey Y AY Trompet Stella S Lopez Lorna M LM Fornage Myriam M Teumer Alexander A Tang Weihong W Rudnicka Alicja R AR Mälarstig Anders A Hottenga Jouke-Jan JJ Kavousi Maryam M Lahti Jari J Tanaka Toshiko T Hayward Caroline C Huffman Jennifer E JE Morange Pierre-Emmanuel PE Rose Lynda M LM Basu Saonli S Rumley Ann A Stott David J DJ Buckley Brendan M BM de Craen Anton J M AJ Sanna Serena S Masala Marco M Biffar Reiner R Homuth Georg G Silveira Angela A Sennblad Bengt B Goel Anuj A Watkins Hugh H Müller-Nurasyid Martina M Rückerl Regina R Taylor Kent K Chen Ming-Huei MH de Geus Eco J C EJ Hofman Albert A Witteman Jacqueline C M JC de Maat Moniek P M MP Palotie Aarno A Davies Gail G Siscovick David S DS Kolcic Ivana I Wild Sarah H SH Song Jaejoon J McArdle Wendy L WL Ford Ian I Sattar Naveed N Schlessinger David D Grotevendt Anne A Franzosi Maria Grazia MG Illig Thomas T Waldenberger Melanie M Lumley Thomas T Tofler Geoffrey H GH Willemsen Gonneke G Uitterlinden André G AG Rivadeneira Fernando F Räikkönen Katri K Chasman Daniel I DI Folsom Aaron R AR Lowe Gordon D GD Westendorp Rudi G J RG Slagboom P Eline PE Cucca Francesco F Wallaschofski Henri H Strawbridge Rona J RJ Seedorf Udo U Koenig Wolfgang W Bis Joshua C JC Mukamal Kenneth J KJ van Dongen Jenny J Widen Elisabeth E Franco Oscar H OH Starr John M JM Liu Kiang K Ferrucci Luigi L Polasek Ozren O Wilson James F JF Oudot-Mellakh Tiphaine T Campbell Harry H Navarro Pau P Bandinelli Stefania S Eriksson Johan J Boomsma Dorret I DI Dehghan Abbas A Clarke Robert R Hamsten Anders A Boerwinkle Eric E Jukema J Wouter JW Naitza Silvia S Ridker Paul M PM Völzke Henry H Deary Ian J IJ Reiner Alexander P AP Trégouët David-Alexandre DA O'Donnell Christopher J CJ Strachan David P DP Peters Annette A Smith Nicholas L NL

PloS one 20141231 12

Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-sc ...[more]

PMID: 25551457

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Project description:BackgroundAlcohol consumption has been associated with increased risks of certain site-specific cancers and decreased risks of some other cancers. There is, however, little reliable evidence as to whether the alcohol-associated risks for specific cancers are modified by smoking, body mass index (BMI) and menopausal hormone therapy (MHT) use.MethodsIn the prospective UK Million Women Study, 1,233,177 postmenopausal women without prior cancer, mean age 56 (SD 5) years, reported their alcohol consumption in median year 1998 (IQR 1998-1999), and were followed by record-linkage for incident cancer. 438,056 women who drank no alcohol or < 1 drink/week were excluded. Cox regression yielded adjusted relative risks (RRs) and 95% confidence intervals (CIs) for 21 cancers by alcohol amount; statistical significance of interactions with smoking, BMI and MHT use was assessed after allowing for multiple testing.ResultsIn 795,121 participants, mean consumption was 6.7 (SD 6.4) alcoholic drinks/week. During 17 (SD 5) years of follow-up, 140,203 incident cancers were recorded. There was strong evidence for a substantial association between alcohol intake and risk of upper aero-digestive cancers (oesophageal squamous cell carcinoma, oral cavity, pharynx and larynx; RR per 1 drink/day = 1.38 [95% CI 1.31-1.46]). There was also strong evidence for more moderate positive associations with breast, colorectal and pancreatic cancer (RRs per 1 drink/day = 1.12 [1.10-1.14], 1.10 [1.07-1.13], 1.08 [1.02-1.13] respectively), and moderate negative associations with thyroid cancer, non-Hodgkin's lymphoma, renal cell carcinoma and multiple myeloma (RRs per 1 drink/day = 0.79 [0.70-0.89], 0.91 [0.86-0.95], 0.88 [0.83-0.94], 0.90 [0.84-0.97] respectively). Significant interactions between alcohol and smoking were seen for upper aero-digestive cancers (RRs per 1 drink/day = 1.66 [1.54-1.79], 1.23 [1.11-1.36], 1.12 [1.01-1.25] in current, past, and never smokers respectively). BMI and MHT did not significantly modify any alcohol-associated risks.ConclusionsThese findings provide robust evidence that greater alcohol intake, even within relatively moderate ranges, increases the risk of cancers of the aerodigestive tract, breast, colorectal and pancreatic cancer, and probably decreases the risk of thyroid cancer, non-Hodgkin's lymphoma, renal cell carcinoma and multiple myeloma. Associations of alcohol intake with cancer risk were not modified by MHT use, adiposity or smoking, except in the case of upper aero-digestive cancers, where the alcohol-associated risk was largely confined to smokers.

Project description:Background: Observational evidence has shown that smoking, alcohol consumption, type 2 diabetes, and body mass index (BMI) are risk factors for peptic ulcer disease (PUD), including gastric ulcer (GU) and duodenal ulcer (DU). However, the observed associations may be confounding factors. Herein, we use Mendelian randomization (MR) to examine causal associations such as smoking, alcohol, type 2 diabetes, BMI, and risks of PUD. Methods: We used 8,17,41,325,82, 231, and 616 identified genetic variants as proxies for age of smoking initiation (AgeSmk), smoking cessation (SmkCes, current/former), number of cigarettes smoked per day (CigDay), smoking status (SmkIni, ever/never), alcohol consumption, type 2 diabetes, and BMI to obtain unconfounded effect estimates on the GU and DU levels among 452,264 participants from the Gene ATLAS. The causal relationship was estimated by using inverse-variance weighted (IVW) as the main method. Sensitivity analysis includes Cochran's Q test, the MR-Egger test, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-robust adjusted profile score (MR-RAPS). In addition, secondary MR analysis was conducted within summary data using genetic risk scores (GRSs) as instrumental variables (IVs). Results: In our two-sample MR analyses, genetic predisposition to smoking (SmkInit) and BMI were associated with an increased risk of GU. The beta values were 0.0035 (95% CI, 0.0021, 0.0049, p = 1.56E-06) for smoking (SmkInit) and 0.0021 (95% CI, 0.0009, 0.0033, p = 0.0008) for BMI. Genetic predisposition to smoking (SmkInit) and higher genetically predicted BMI were associated with an increased risk of DU. The beta values of DU were 0.0029 (95% CI, 0.0017, 0.0041, p = 2.43E-06) for smoking (SmkInit) and 0.0018 (95% CI, 0.0007, 0.0029, p = 0.001) for BMI. No other causal association between smoking (AgeSmk, CigDay, and SmkCes), alcohol consumption, type 2 diabetes, and GU or DU was observed. Consistent results were obtained in sensitivity analyses. Furthermore, the GRS approach showed similar results in the several MR methods. Conclusion: These findings do not support a causal role of AgeSmk, CigDay, SmkCes, alcohol consumption, and type 2 diabetes in the development of GU and DU. However, it is confirmed that SmkInit and BMI have a causal part in the development of GU and DU.

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Dataset Information

No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.

Publications

No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.

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