Abstract：
Cognitive decline, and more specifically Alzheimer\'s disease, continues to increase in prevalence globally, with few, if any, adequate preventative approaches. Several tests of cognition are utilized in the diagnosis of cognitive decline that assess executive function, short- and long-term memory, cognitive flexibility, and speech and motor control. Recent studies have separately investigated the genetic component of both cognitive health, using these measures, and circulating fatty acids.
We aimed to examine the potential moderating effect of main species of ω-3 polyunsaturated fatty acids (PUFAs) on an individual\'s genetically conferred risk of cognitive decline.
The Offspring cohort from the Framingham Heart Study was cross-sectionally analyzed in this genome-wide interaction study (GWIS). Our sample included all individuals with red blood cell ω-3 PUFA, genetic, cognitive testing (via Trail Making Tests [TMTs]), and covariate data (N = 1620). We used linear mixed effects models to predict each of the 3 cognitive measures (TMT A, TMT B, and TMT D) by each ω-3 PUFA, single nucleotide polymorphism (SNP) (0, 1, or 2 minor alleles), ω-3 PUFA by SNP interaction term, and adjusting for sex, age, education, APOE ε4 genotype status, and kinship (relatedness).
Our analysis identified 31 unique SNPs from 24 genes reaching an exploratory significance threshold of 1×10-5. Fourteen of the 24 genes have been previously associated with the brain/cognition, and 5 genes have been previously associated with circulating lipids. Importantly, 8 of the genes we identified, DAB1, SORCS2, SERINC5, OSBPL3, CPA6, DLG2, MUC19, and RGMA, have been associated with both cognition and circulating lipids. We identified 22 unique SNPs for which individuals with the minor alleles benefit substantially from increased ω-3 fatty acid concentrations and 9 unique SNPs for which the common homozygote benefits.
In this GWIS of ω-3 PUFA species on cognitive outcomes, we identified 8 unique genes with plausible biology suggesting individuals with specific polymorphisms may have greater potential to benefit from increased ω-3 PUFA intake. Additional replication in prospective settings with more diverse samples is needed.
We aimed to examine the potential moderating effect of main species of ω-3 polyunsaturated fatty acids (PUFAs) on an individual\'s genetically conferred risk of cognitive decline.
The Offspring cohort from the Framingham Heart Study was cross-sectionally analyzed in this genome-wide interaction study (GWIS). Our sample included all individuals with red blood cell ω-3 PUFA, genetic, cognitive testing (via Trail Making Tests [TMTs]), and covariate data (N = 1620). We used linear mixed effects models to predict each of the 3 cognitive measures (TMT A, TMT B, and TMT D) by each ω-3 PUFA, single nucleotide polymorphism (SNP) (0, 1, or 2 minor alleles), ω-3 PUFA by SNP interaction term, and adjusting for sex, age, education, APOE ε4 genotype status, and kinship (relatedness).
Our analysis identified 31 unique SNPs from 24 genes reaching an exploratory significance threshold of 1×10-5. Fourteen of the 24 genes have been previously associated with the brain/cognition, and 5 genes have been previously associated with circulating lipids. Importantly, 8 of the genes we identified, DAB1, SORCS2, SERINC5, OSBPL3, CPA6, DLG2, MUC19, and RGMA, have been associated with both cognition and circulating lipids. We identified 22 unique SNPs for which individuals with the minor alleles benefit substantially from increased ω-3 fatty acid concentrations and 9 unique SNPs for which the common homozygote benefits.
In this GWIS of ω-3 PUFA species on cognitive outcomes, we identified 8 unique genes with plausible biology suggesting individuals with specific polymorphisms may have greater potential to benefit from increased ω-3 PUFA intake. Additional replication in prospective settings with more diverse samples is needed.
摘要：
背景：认知衰退，更具体地说，阿尔茨海默病，全球患病率继续上升，很少，如果有的话,适当的预防方法。几种认知测试用于评估执行功能的认知衰退的诊断，短期和长期记忆，认知灵活性，语音和运动控制。最近的研究分别调查了认知健康的遗传成分，使用这些措施，和循环脂肪酸。
目的：我们将研究主要物种ω3多不饱和脂肪酸（PUFA）对个体遗传赋予的认知下降风险的潜在调节作用。
方法：在这项全基因组相互作用研究（GWIS）中，对弗雷明汉心脏研究的后代队列进行了横断面分析。我们的样本包括所有红细胞ω3-PUFA的个体，遗传,认知测试(通过跟踪测试)，和协变量数据(N=1,620)。我们使用线性混合效应模型来预测三种认知测量中的每一种(TMT-A，TMT-B,TMT-D)由每个ω3-PUFA，单核苷酸多态性（SNP）（0，1或2个次要等位基因），ω3-PUFA通过SNP相互作用项，适应性，年龄,教育,APOE-ε4基因型状态和亲缘关系(亲缘关系)。
结果：我们的分析从24个基因中鉴定出31个独特的SNP，达到1×10-5的探索性意义阈值。24个基因中的14个先前与大脑/认知相关，5个基因先前与循环脂质相关。重要的是,我们鉴定的8个基因：DAB1，SORCS2，SERINC5，OSBPL3，CPA6，DLG2，MUC19和RGMA与认知和循环脂质有关。我们确定了22个独特的SNP，其中具有次要等位基因的个体从增加的ω3脂肪酸水平中实质性受益，以及9个独特的SNP，普通纯合子受益。
结论：在ω3-PUFA物种对认知结果的GWIS中，我们鉴定出8个具有合理生物学特性的独特基因,提示具有特定多态性的个体可能有更大的潜力从ω3-PUFA摄入增加中获益.需要在具有更多样化样品的预期环境中进行额外的复制。
目的：我们将研究主要物种ω3多不饱和脂肪酸（PUFA）对个体遗传赋予的认知下降风险的潜在调节作用。
方法：在这项全基因组相互作用研究（GWIS）中，对弗雷明汉心脏研究的后代队列进行了横断面分析。我们的样本包括所有红细胞ω3-PUFA的个体，遗传,认知测试(通过跟踪测试)，和协变量数据(N=1,620)。我们使用线性混合效应模型来预测三种认知测量中的每一种(TMT-A，TMT-B,TMT-D)由每个ω3-PUFA，单核苷酸多态性（SNP）（0，1或2个次要等位基因），ω3-PUFA通过SNP相互作用项，适应性，年龄,教育,APOE-ε4基因型状态和亲缘关系(亲缘关系)。
结果：我们的分析从24个基因中鉴定出31个独特的SNP，达到1×10-5的探索性意义阈值。24个基因中的14个先前与大脑/认知相关，5个基因先前与循环脂质相关。重要的是,我们鉴定的8个基因：DAB1，SORCS2，SERINC5，OSBPL3，CPA6，DLG2，MUC19和RGMA与认知和循环脂质有关。我们确定了22个独特的SNP，其中具有次要等位基因的个体从增加的ω3脂肪酸水平中实质性受益，以及9个独特的SNP，普通纯合子受益。
结论：在ω3-PUFA物种对认知结果的GWIS中，我们鉴定出8个具有合理生物学特性的独特基因,提示具有特定多态性的个体可能有更大的潜力从ω3-PUFA摄入增加中获益.需要在具有更多样化样品的预期环境中进行额外的复制。
