Evidence map›Paper›PMID 35692035›Full record

ArticleBMC medicine2022

Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants.

Maria Carolina Borges, Philip C Haycock, Jie Zheng, Gibran Hemani, Michael V Holmes, George Davey Smith, Aroon D Hingorani, Deborah A Lawlor

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 4 pooled it
24.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

105 citing papers in PubMed, 4 syntheses or guidelines pooled it, 195 citations in OpenAlex.

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45 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Maria Carolina BorgesMRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK. m.c.borges@bristol.ac.uk.
Philip C HaycockMRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Jie ZhengMRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Gibran HemaniMRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Michael V HolmesMRC Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
George Davey SmithMRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Aroon D HingoraniInstitute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK.
Deborah A LawlorMRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
University of Bristol · GBNIHR Bristol Biomedical Research Centre · GBSLAC National Accelerator Laboratory · USUniversity of Oxford · GB

Funding

British Heart Foundation CH/F/20/90003British Heart Foundation FS/18/23/33512Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MC_UU_00011/1Medical Research Council MC_UU_00011/4Medical Research Council MC_UU_00011/6Medical Research Council MC_UU_00011/7Medical Research Council MR/V033867/1Wellcome Trust 208806/Z/17/Z
6 · The paper itself

Abstract

backgroundDespite early interest in the health effects of polyunsaturated fatty acids (PUFA), there is still substantial controversy and uncertainty on the evidence linking PUFA to cardiovascular diseases (CVDs). We investigated the effect of plasma concentration of omega-3 PUFA (i.e. docosahexaenoic acid (DHA) and total omega-3 PUFA) and omega-6 PUFA (i.e. linoleic acid and total omega-6 PUFA) on the risk of CVDs using Mendelian randomization.

methodsWe conducted the largest genome-wide association study (GWAS) of circulating PUFA to date including a sample of 114,999 individuals and incorporated these data in a two-sample Mendelian randomization framework to investigate the involvement of circulating PUFA on a wide range of CVDs in up to 1,153,768 individuals of European ancestry (i.e. coronary artery disease, ischemic stroke, haemorrhagic stroke, heart failure, atrial fibrillation, peripheral arterial disease, aortic aneurysm, venous thromboembolism and aortic valve stenosis).

resultsGWAS identified between 46 and 64 SNPs for the four PUFA traits, explaining 4.8-7.9% of circulating PUFA variance and with mean F statistics >100. Higher genetically predicted DHA (and total omega-3 fatty acids) concentration was related to higher risk of some cardiovascular endpoints; however, these findings did not pass our criteria for multiple testing correction and were attenuated when accounting for LDL-cholesterol through multivariable Mendelian randomization or excluding SNPs in the vicinity of the FADS locus. Estimates for the relation between higher genetically predicted linoleic acid (and total omega-6) concentration were inconsistent across different cardiovascular endpoints and Mendelian randomization methods. There was weak evidence of higher genetically predicted linoleic acid being related to lower risk of ischemic stroke and peripheral artery disease when accounting by LDL-cholesterol.

conclusionsWe have conducted the largest GWAS of circulating PUFA to date and the most comprehensive Mendelian randomization analyses. Overall, our Mendelian randomization findings do not support a protective role of circulating PUFA concentration on the risk of CVDs. However, horizontal pleiotropy via lipoprotein-related traits could be a key source of bias in our analyses.

Indexed as

Cardiovascular DiseasesIschemic StrokeBiological Specimen BanksCholesterol, LDLFatty AcidsFatty Acids, UnsaturatedGenome-Wide Association StudyHumansLinoleic AcidMendelian Randomization AnalysisPolymorphism, Single NucleotideRisk FactorsUnited KingdomCholesterol, LDLFatty AcidsFatty Acids, UnsaturatedLinoleic AcidCardiovascular diseasesFatty acidsMendelian randomization

Identifiers

PMID35692035
PMCPMC9190170
OpenAlexW4282549953

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.