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:ImportanceAdvanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD.ObjectiveTo assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD.Design, setting, participantsThis study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies. Summary-level statistics for these instruments were obtained for advanced AMD from the International AMD Genomics Consortium 2016 data set, which consisted of 16 144 individuals with AMD and 17 832 control individuals. Data were analyzed from July 2020 to September 2021.ExposuresSmoking initiation, smoking cessation, lifetime smoking, age at smoking initiation, alcoholic drinks per week, body mass index, systolic and diastolic blood pressure, type 2 diabetes, glycated hemoglobin, fasting glucose, and fasting insulin.Main outcomes and measuresAdvanced AMD and its subtypes, geographic atrophy (GA), and neovascular AMD.ResultsA 1-SD increase in logodds of genetically predicted smoking initiation was associated with higher risk of advanced AMD (odds ratio [OR], 1.26; 95% CI, 1.13-1.40; P < .001), while a 1-SD increase in logodds of genetically predicted smoking cessation (former vs current smoking) was associated with lower risk of advanced AMD (OR, 0.66; 95% CI, 0.50-0.87; P = .003). Genetically predicted increased lifetime smoking was associated with increased risk of advanced AMD (OR per 1-SD increase in lifetime smoking behavior, 1.32; 95% CI, 1.09-1.59; P = .004). Genetically predicted alcohol consumption was associated with higher risk of GA (OR per 1-SD increase of log-transformed alcoholic drinks per week, 2.70; 95% CI, 1.48-4.94; P = .001). There was insufficient evidence to suggest that genetically predicted blood pressure, body mass index, and glycemic traits were associated with advanced AMD.Conclusions and relevanceThis study provides genetic evidence that increased alcohol intake may be a causal risk factor for GA. As there are currently no known treatments for GA, this finding has important public health implications. These results also support previous observational studies associating smoking behavior with risk of advanced AMD, thus reinforcing existing public health messages regarding the risk of blindness associated with smoking.

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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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