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Omega-3 Fatty Acids Interact with DPP10 Region Genotype in Association with Childhood Atopy.

ABSTRACT: Associations of omega-3 fatty acids (n-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 n-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 n-3 was derived from food frequency questionnaires and plasma n-3 was measured via untargeted mass spectrometry in early childhood and children aged 6 years old. Interactions of genotype with n-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 DPP10 (rs958457 and rs1516311) interacted with plasma n-3 at age 3 years in VDAART (p = 0.007 and 0.003, respectively) and with plasma n-3 at age 18 months in COPSAC (p = 0.01 and 0.02, respectively) in associationwith atopy. Another DPP10 region SNP, rs1367180, interacted with dietary n-3 at age 6 years in VDAART (p = 0.009) and with plasma n-3 at age 6 years in COPSAC (p = 0.004) in association with atopy. No replicated interactions were identified for asthma. The effect of n-3 on reducing childhood allergic disease may differ by individual factors, including genetic variation in the DPP10 region.

SUBMITTER: Lee-Sarwar KA

PROVIDER: S-EPMC10223962 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Omega-3 Fatty Acids Interact with DPP10 Region Genotype in Association with Childhood Atopy.

Lee-Sarwar Kathleen A KA Fischer-Rasmussen Kasper K Bønnelykke Klaus K Bisgaard Hans H Chawes Bo B Kelly Rachel S RS Lasky-Su Jessica J Zeiger Robert S RS O'Connor George T GT Bacharier Leonard B LB Carey Vincent J VJ Laranjo Nancy N Litonjua Augusto A AA Weiss Scott T ST

Nutrients 20230522 10

Associations of omega-3 fatty acids (n-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 n-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 n-3 was derived from food frequency questionnaires and plasma n-3 was me ...[more]

PMID: 37242299

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Project description:BackgroundOmega-3 and omega-6 may be protective factors for cholelithiasis. However, this relationship has not yet been demonstrated clearly. Therefore, we attempted to identify these causal relationships.Materials and methodsThe omega-3/6 fatty acid discovery dataset was obtained from UK Biobank and contained 114,999 individuals. The validation set was derived from an independent genome-wide association study (GWAS) and contained 13,544 individuals. The cholelithiasis dataset was derived from FinnGen and contained 19,023 cases and 195,144 controls. The inverse variance weighting (IVW) method was used as the main method of analysis in this study. Multiple methods of analysis were also used in the repeated methods, including the MR-Egger, weighted median, MR-pleiotropic residual sum (MR-PRESSO), outliers, and maximum likelihood methods. In addition, we used multiple sensitivity analyses to identify the potential pleiotropy.ResultIn the discovery stage, the results of the random effect IVW analysis showed that higher omega-3 levels were correlated inversely with the risk of cholelithiasis (β = -0.22, 95% CI [-0.32 to -0.12], P = 1.49 × 10-5). When the replication analysis was performed using another set of instrumental variables (IVs), the causal relationship between omega-3 fatty acids and cholelithiasis remained stable (β = -0.42, 95% CI [-0.66 to -0.18], P = 5.49 × 10-4), except for the results obtained using the MR-Egger method, which were not significant. The results of the IVW approach showed that each SD increase in omega-6 levels was associated negatively with the risk of cholelithiasis, both in the discovery (β = -0.21, 95% CI [-0.35 to -0.06], P = 4.37 × 10-3) and the validation phases (β = -0.21, 95% CI [-0.40 to -0.02], P = 3.44 × 10-2).ConclusionThe results of our MR study suggest that omega-3/6 is associated with cholelithiasis risk. Attention to the risk of cholelithiasis in individuals with low serum omega-3/6 levels is necessary.

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Omega-3 Fatty Acids Interact with DPP10 Region Genotype in Association with Childhood Atopy.

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Omega-3 Fatty Acids Interact with <i>DPP10</i> Region Genotype in Association with Childhood Atopy.

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Omega-3 Fatty Acids Interact with DPP10 Region Genotype in Association with Childhood Atopy.

Publications

Omega-3 Fatty Acids Interact with &lt;i&gt;DPP10&lt;/i&gt; Region Genotype in Association with Childhood Atopy.

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Omega-3 Fatty Acids Interact with <i>DPP10</i> Region Genotype in Association with Childhood Atopy.