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

Dariush Mozaffarian, Hassan S. Dashti, Mary K. Wojczynski, Audrey Y. Chu, Jennifer A. Nettleton, Satu Männistö, Kati Kristiansson, Mägi Reedik, Jari Lahti, Denise K. Houston, Marilyn C. Cornelis, Frank J.A. Van Rooij, Maria Dimitriou, Stavroula Kanoni, Vera Mikkilä, Lyn M. Steffen, Marcia C. De Oliveira Otto, Lu Qi, Bruce Psaty, Luc DjousseJerome I. Rotter, Kennet Harald, Markus Perola, Harri Rissanen, Antti Jula, Fischer Krista, Evelin Mihailov, Mary F. Feitosa, Julius S. Ngwa, Luting Xue, Paul F. Jacques, Mia Maria Perälä, Aarno Palotie, Yongmei Liu, Nike A. Nalls, Luigi Ferrucci, Dena Hernandez, Ani Manichaikul, Michael Y. Tsai, Jessica C. Kiefte-De Jong, Albert Hofman, André G. Uitterlinden, Loukianos Rallidis, Paul M. Ridker, Lynda M. Rose, Julie E. Buring, Terho Lehtimäki, Mika Kähönen, Jorma Viikari, Rozenn Lemaitre, Veikko Salomaa, Paul Knekt, Andres Metspalu, Ingrid B. Borecki, L. Adrienne Cupples, Johan G. Eriksson, Stephen B. Kritchevsky, Stefania Bandinelli, David Siscovick, Oscar H. Franco, Panos Deloukas, George Dedoussis, Daniel I. Chasman, Olli Raitakari, Toshiko Tanaka

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17 Scopus citations


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.

Original languageEnglish
Article numbere0186456
JournalPloS one
Issue number12
StatePublished - Dec 2017


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