Mozaffarian Dariush, Dashti Hassan S, Wojczynski Mary K, Chu Audrey Y, Nettleton Jennifer A, Männistö Satu, Kristiansson Kati, Reedik Mägi, Lahti Jari, Houston Denise K, Cornelis Marilyn C, van Rooij Frank J A, Dimitriou Maria, Kanoni Stavroula, Mikkilä Vera, Steffen Lyn M, de Oliveira Otto Marcia C, Qi Lu, Psaty Bruce, Djousse Luc, Rotter Jerome I, Harald Kennet, Perola Markus, Rissanen Harri, Jula Antti, Krista Fischer, Mihailov Evelin, Feitosa Mary F, Ngwa Julius S, Xue Luting, Jacques Paul F, Perälä Mia-Maria, Palotie Aarno, Liu Yongmei, Nalls Nike A, Ferrucci Luigi, Hernandez Dena, Manichaikul Ani, Tsai Michael Y, Kiefte-de Jong Jessica C, Hofman Albert, Uitterlinden André G, Rallidis Loukianos, Ridker Paul M, Rose Lynda M, Buring Julie E, Lehtimäki Terho, Kähönen Mika, Viikari Jorma, Lemaitre Rozenn, Salomaa Veikko, Knekt Paul, Metspalu Andres, Borecki Ingrid B, Cupples L Adrienne, Eriksson Johan G, Kritchevsky Stephen B, Bandinelli Stefania, Siscovick David, Franco Oscar H, Deloukas Panos, Dedoussis George, Chasman Daniel I, Raitakari Olli, Tanaka Toshiko
Friedman School of Nutrition Science & Policy, Tufts University, Boston, MA, United States of America.
Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, United States of America.
PLoS One. 2017 Dec 13;12(12):e0186456. doi: 10.1371/journal.pone.0186456. eCollection 2017.
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.
To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption.
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.
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.
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.
经常食用鱼类和摄入ω-3脂肪酸可能对健康有诸多益处，主要饮食指南也推荐这样做。然而，鱼类和ω-3脂肪酸的摄入量在人群内部和不同人群之间仍存在显著差异，这可能部分归因于遗传影响。
识别影响鱼类及膳食中二十碳五烯酸加二十二碳六烯酸（EPA+DHA）摄入量的常见基因变异。
我们对来自CHARGE（基因组流行病学心脏与衰老研究队列）联盟营养工作组的17个欧洲裔队列中的鱼类摄入量（n = 86,467）和EPA+DHA摄入量（n = 62,265）进行了全基因组关联（GWA）荟萃分析。针对鱼类和EPA+DHA摄入量的队列特异性GWA分析（加性模型）结果，根据年龄、性别、能量摄入和人群分层进行了调整，并使用具有逆方差权重的固定效应荟萃分析（METAL软件）分别进行荟萃分析。此外，在2个队列中估计了遗传力。
鱼类和EPA+DHA摄入量的遗传力估计值分别为0.13 - 0.24和0.12 - 0.22。在6号染色体上观察到rs9502823与鱼类摄入量存在显著的全基因组关联：次要等位基因的每个拷贝（FreqA = 0.015）与每日鱼类摄入量降低0.029份（约每月1份）相关（P = 1.96×10 - 8）。虽然肥胖相关的FTO基因中的rs7206790位列关联度最高的基因之一（P = 8.18×10 - 7），但未观察到与EPA+DHA有显著关联。事后计算表明，检测到与鱼类效应大小为0.05%、EPA+DHA效应大小为0.08%相关的基因变异的统计功效为95%。
这些新发现表明，非遗传的个人和环境因素是鱼类摄入量显著差异的主要决定因素，是增加所有人摄入量的可改变目标。rs72838923处信号的潜在基因以及关联机制值得进一步研究。
