ArticleMolecular biology and evolution2016
Positive Selection on a Regulatory Insertion-Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid.
Article in Molecular biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 107 citations in OpenAlex.
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- A 12-Week Randomized Intervention Comparing the Healthy US, Mediterranean, and Vegetarian Dietary Patterns of the US Dietary Guidelines for Changes in Body Weight, Hemoglobin A1c, Blood Pressure, and Dietary Quality among African American Adults.The Journal of nutrition · 2023Trial
- Statin therapy upregulates arachidonic acid status via enhanced endogenous synthesis in patients with plaque psoriasis.Prostaglandins, leukotrienes, and essential fatty acids · 2022Trial
- Prospective clinical trial examining the impact of genetic variation in FADS1 on the metabolism of linoleic acid- and ɣ-linolenic acid-containing botanical oils.The American journal of clinical nutrition · 2020Trial
- Allele frequency trajectories across age groups reveal ongoing natural selection shaping disease susceptibility.American journal of human genetics · 2026Article
- DHA: Nutritional Programming During the First 1000 Days of Life.Nutrients · 2026Review
- Recipient plasma metabolomics as a predictor of heart transplant severe primary graft dysfunction.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Hypothesis: the rs66698963 insertion-deletion alters the AA/EPA ratio and cardiovascular disease risk.Lipids in health and disease · 2026Review
- Molecular Insights into the Functional Roles of Variants in the <italic>FADS</italic> Gene Cluster on Omega-3 Long-Chain Polyunsaturated Fatty Acid Synthesis.Lifestyle genomics · 2026Review
- The Diet Guidelines: 3 Diets (DG3D) study protocol of a behavioral teaching kitchen intervention for type-2 diabetes prevention among African American adults.Contemporary clinical trials · 2025Article
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- Arachidonic acid as a potentially critical nutrient for vegetarians and vegans - position paper of the Research Institute for Plant-based Nutrition (IFPE).Lipids in health and disease · 2025Review
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- Population genomics advances in frontier ethnic minorities in China.Science China. Life sciences · 2025Review
- Genetic diversity and dietary adaptations of the Central Plains Han Chinese population in East Asia.Communications biology · 2025Article
- Precision nutrition across climates: decoding diet, tradition, and genomic adaptations from South Asia to the Arctic.Frontiers in nutrition · 2025Review
- Phenome-wide association study of population-differentiating genetic variants around geneEvolution, medicine, and public health · 2024Article
- Exploring the genetic diversity of the Japanese population: Insights from a large-scale whole genome sequencing analysis.PLoS genetics · 2023Article
- Shared genetic basis informs the roles of polyunsaturated fatty acids in brain disorders.medRxiv : the preprint server for health sciences · 2023Article
- Genetics of vegetarianism: A genome-wide association study.PloS one · 2023Article
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14 authors at 3 institutions in 2 countries.
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Abstract
Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22-bp insertion-deletion within FADS2, is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro. Here, we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the US. A much higher I/I genotype frequency was found in Indians (68%) than in the US (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum, and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African, and some East Asian populations. Basal plasma phospholipid arachidonic acid (ARA) status was 8% greater in I/I compared with D/D individuals. The biochemical pathway product-precursor difference, ARA minus linoleic acid, was 31% and 13% greater for I/I and I/D compared with D/D, respectively. This study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice.
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