Dataset Information

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.

ABSTRACT:

Background

Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences.

Objective

To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption.

Design

We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts.

Results

Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA.

Conclusions

These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.

SUBMITTER: Mozaffarian D

PROVIDER: S-EPMC5728559 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.

Mozaffarian Dariush D Dashti Hassan S HS Wojczynski Mary K MK Chu Audrey Y AY Nettleton Jennifer A JA Männistö Satu S Kristiansson Kati K Reedik Mägi M Lahti Jari J Houston Denise K DK Cornelis Marilyn C MC van Rooij Frank J A FJA Dimitriou Maria M Kanoni Stavroula S Mikkilä Vera V Steffen Lyn M LM de Oliveira Otto Marcia C MC Qi Lu L Psaty Bruce B Djousse Luc L Rotter Jerome I JI Harald Kennet K Perola Markus M Rissanen Harri H Jula Antti A Krista Fischer F Mihailov Evelin E Feitosa Mary F MF Ngwa Julius S JS Xue Luting L Jacques Paul F PF Perälä Mia-Maria MM Palotie Aarno A Liu Yongmei Y Nalls Nike A NA Ferrucci Luigi L Hernandez Dena D Manichaikul Ani A Tsai Michael Y MY Kiefte-de Jong Jessica C JC Hofman Albert A Uitterlinden André G AG Rallidis Loukianos L Ridker Paul M PM Rose Lynda M LM Buring Julie E JE Lehtimäki Terho T Kähönen Mika M Viikari Jorma J Lemaitre Rozenn R Salomaa Veikko V Knekt Paul P Metspalu Andres A Borecki Ingrid B IB Cupples L Adrienne LA Eriksson Johan G JG Kritchevsky Stephen B SB Bandinelli Stefania S Siscovick David D Franco Oscar H OH Deloukas Panos P Dedoussis George G Chasman Daniel I DI Raitakari Olli O Tanaka Toshiko T

PloS one 20171213 12

<h4>Background</h4>Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences.<h4>Objective</h4>To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption.<h4>Design</h4>We conducted genome-wide association (GWA) meta-analysis of fish ...[more]

PMID: 29236708

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Project description:Aims/hypothesisType 2 diabetes is a complex metabolic disease with increasing prevalence worldwide. Improving the prediction of incident type 2 diabetes using epigenetic markers could help tailor prevention efforts to those at the highest risk. The aim of this study was to identify predictive methylation markers for incident type 2 diabetes by combining epigenome-wide association study (EWAS) results from five prospective European cohorts.MethodsWe conducted a meta-analysis of EWASs in blood collected 7-10 years prior to type 2 diabetes diagnosis. DNA methylation was measured with Illumina Infinium Methylation arrays. A total of 1250 cases and 1950 controls from five longitudinal cohorts were included: Doetinchem, ESTHER, KORA1, KORA2 and EPIC-Norfolk. Associations between DNA methylation and incident type 2 diabetes were examined using robust linear regression with adjustment for potential confounders. Inverse-variance fixed-effects meta-analysis of cohort-level individual CpG EWAS estimates was performed using METAL. The methylGSA R package was used for gene set enrichment analysis. Confirmation of genome-wide significant CpG sites was performed in a cohort of Indian Asians (LOLIPOP, UK).ResultsThe meta-analysis identified 76 CpG sites that were differentially methylated in individuals with incident type 2 diabetes compared with control individuals (p values <1.1 × 10-7). Sixty-four out of 76 (84.2%) CpG sites were confirmed by directionally consistent effects and p values <0.05 in an independent cohort of Indian Asians. However, on adjustment for baseline BMI only four CpG sites remained genome-wide significant, and addition of the 76 CpG methylation risk score to a prediction model including established predictors of type 2 diabetes (age, sex, BMI and HbA1c) showed no improvement (AUC 0.757 vs 0.753). Gene set enrichment analysis of the full epigenome-wide results clearly showed enrichment of processes linked to insulin signalling, lipid homeostasis and inflammation.Conclusions/interpretationBy combining results from five European cohorts, and thus significantly increasing study sample size, we identified 76 CpG sites associated with incident type 2 diabetes. Replication of 64 CpGs in an independent cohort of Indian Asians suggests that the association between DNA methylation levels and incident type 2 diabetes is robust and independent of ethnicity. Our data also indicate that BMI partly explains the association between DNA methylation and incident type 2 diabetes. Further studies are required to elucidate the underlying biological mechanisms and to determine potential causal roles of the differentially methylated CpG sites in type 2 diabetes development.

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Dataset Information

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.

Background

Objective

Design

Results

Conclusions

Publications

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.

Similar Datasets

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