| Summary: | Associations of omega-3 fatty acids (<i>n</i>-3) with allergic diseases are inconsistent, perhaps in part due to genetic variation. We sought to identify and validate genetic variants that modify associations of <i>n</i>-3 with childhood asthma or atopy in participants in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC). Dietary <i>n</i>-3 was derived from food frequency questionnaires and plasma <i>n</i>-3 was measured via untargeted mass spectrometry in early childhood and children aged 6 years old. Interactions of genotype with <i>n</i>-3 in association with asthma or atopy at age 6 years were sought for six candidate genes/gene regions and genome-wide. Two SNPs in the region of <i>DPP10</i> (rs958457 and rs1516311) interacted with plasma <i>n</i>-3 at age 3 years in VDAART (<i>p</i> = 0.007 and 0.003, respectively) and with plasma <i>n</i>-3 at age 18 months in COPSAC (<i>p</i> = 0.01 and 0.02, respectively) in associationwith atopy. Another <i>DPP10</i> region SNP, rs1367180, interacted with dietary <i>n</i>-3 at age 6 years in VDAART (<i>p</i> = 0.009) and with plasma <i>n</i>-3 at age 6 years in COPSAC (<i>p</i> = 0.004) in association with atopy. No replicated interactions were identified for asthma. The effect of <i>n</i>-3 on reducing childhood allergic disease may differ by individual factors, including genetic variation in the <i>DPP10</i> region.
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