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. 2017 Dec 13;12(12):e0186456.
doi: 10.1371/journal.pone.0186456. eCollection 2017.

Genome-wide Association Meta-Analysis of Fish and EPA+DHA Consumption in 17 US and European Cohorts

Dariush Mozaffarian  1 Hassan S Dashti  1   2 Mary K Wojczynski  3 Audrey Y Chu  4 Jennifer A Nettleton  5 Satu Männistö  6 Kati Kristiansson  6 Mägi Reedik  7 Jari Lahti  8   9 Denise K Houston  10 Marilyn C Cornelis  11 Frank J A van Rooij  12   13 Maria Dimitriou  14 Stavroula Kanoni  15 Vera Mikkilä  16   17 Lyn M Steffen  18 Marcia C de Oliveira Otto  5 Lu Qi  13 Bruce Psaty  19 Luc Djousse  20 Jerome I Rotter  21 Kennet Harald  6 Markus Perola  6   22   23 Harri Rissanen  6 Antti Jula  6 Fischer Krista  7 Evelin Mihailov  7 Mary F Feitosa  3 Julius S Ngwa  24   25 Luting Xue  24 Paul F Jacques  1   26 Mia-Maria Perälä  27 Aarno Palotie  22   28 Yongmei Liu  29 Nike A Nalls  30 Luigi Ferrucci  31 Dena Hernandez  30 Ani Manichaikul  32 Michael Y Tsai  33 Jessica C Kiefte-de Jong  12   34 Albert Hofman  12   13   35 André G Uitterlinden  12   13 Loukianos Rallidis  36 Paul M Ridker  6   37 Lynda M Rose  4 Julie E Buring  4   37 Terho Lehtimäki  38 Mika Kähönen  39 Jorma Viikari  40 Rozenn Lemaitre  41 Veikko Salomaa  6 Paul Knekt  6 Andres Metspalu  7 Ingrid B Borecki  3 L Adrienne Cupples  24   42 Johan G Eriksson  6   43   44 Stephen B Kritchevsky  10 Stefania Bandinelli  45 David Siscovick  46 Oscar H Franco  12   13 Panos Deloukas  15   47 George Dedoussis  14 Daniel I Chasman  4   37 Olli Raitakari  17   48 Toshiko Tanaka  31
Free PMC article

Genome-wide Association Meta-Analysis of Fish and EPA+DHA Consumption in 17 US and European Cohorts

Dariush Mozaffarian et al. PLoS One. .
Free PMC article


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.

Conflict of interest statement

Competing Interests: Luc Djousse reports receiving investigator-initiated grants (omega-3 fatty acid studies) from NIH and Amarin Pharma, Inc. Currently serving as ad hoc consultant for Amarin Pharma, Inc. Bruce Psaty reports serving on the DSMB of a clinical trial for a device funded by the manufacturer (Zoll LifeCor) and on the Steering Committee for the Yale Open Data Access Project funded by Johnson & Johnson." Paul Ridker has received research grant funds from AstraZeneca, a manufacturer of a prescription fish oil product. Oscar Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.); Metagenics Inc.; and AXA. Nestlé Nutrition (Nestec Ltd.); Metagenics Inc.; and AXA had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript. Dr. Mozaffarian reports reports ad hoc honoraria or consulting from Bunge, Haas Avocado Board, Nutrition Impact, Amarin, Astra Zeneca, Boston Heart Diagnostics, GOED, and Life Sciences Research Organization; and scientific advisory boards, Unilever North America and Elysium Health.Harvard University holds a patent, listing Dr. Mozaffarian as one of three co-inventors, for use of trans-palmitoleic acid to prevent and treat insulin resistance, type 2 diabetes, and related conditions. All other authors report no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.


Fig 1
Fig 1. Regional association plot.
The figures display–log10 p-values for SNPs within the locus of highest significance for the analysis of fish consumption (top panel) and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) consumption (bottom panel). The degree of linkage disequilibrium (r2) is displayed in gradients of gray from dark (low linkage) to light (high linkage).

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