Associations of genetically predicted fatty acid levels across the phenome: A mendelian randomisation study

Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of th...

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Veröffentlicht in:PLoS medicine Jg. 19; H. 12; S. e1004141
Hauptverfasser: Zagkos, Loukas, Dib, Marie-Joe, Pinto, Rui, Gill, Dipender, Koskeridis, Fotios, Drenos, Fotios, Markozannes, Georgios, Elliott, Paul, Zuber, Verena, Tsilidis, Kostas, Dehghan, Abbas, Tzoulaki, Ioanna
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 29.12.2022
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ISSN:1549-1676, 1549-1277, 1549-1676
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Abstract Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes. The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed. Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.
AbstractList Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes. The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed. Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.
Background Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes. Methods and findings The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed. Conclusions Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention. Loukas Zagkos and colleagues conduct Mendelian randomisation analysis to investigate potential causal associations of circulating fatty acids and 845 disease outcomes in the UK Biobank. Author summary Why was this study done? Epidemiological studies have investigated the influence of dietary fatty acids on several chronic diseases including cardiovascular disease (CVD), inflammatory diseases, cancers, and neurodegenerative conditions. The evidence is conflicting and inconclusive and is not supported by randomised controlled trials (RCTs) on fatty acids supplementation. The fact that the human fatty acid metabolome partly reflects the fatty acid intake was leveraged in this work. What did the researchers do and find? Mendelian randomisation analysis was conducted to investigate potential causal associations of circulating fatty acids and 845 disease outcomes in UK Biobank. We found that 1 mmol/L increase in genetically predicted docosahexaenoic acid (DHA) was associated with 24% reduced odds of cholelithiasis and cholecystitis, as well as 17% reduced odds of obesity. One mmol/L higher genetically predicted linoleic acid (LA) was associated with 27% increased odds of ischemic heart disease. When assessed with other fatty acid classes simultaneously, 1 mmol/L higher genetically predicted LA and omega-6 fatty acids were associated with higher odds of coronary heart disease (64% and 81% increase, respectively). What do these findings mean? Our results support the prioritisation of RCTs examining the role of primary and secondary prevention of cholelithiasis via dietary modification or supplementation of DHA and other omega-3 fatty acids. Our principal findings also provide evidence against the supplemental use of fatty acids for CVD prevention. Triangulation of evidence for causal inference of fatty acid levels through experimental studies susceptible to different assumptions is needed to strengthen the evidence.
Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes. The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed. Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.
Loukas Zagkos and colleagues conduct Mendelian randomisation analysis to investigate potential causal associations of circulating fatty acids and 845 disease outcomes in the UK Biobank.
Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes.BACKGROUNDFatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes.The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed.METHODS AND FINDINGSThe UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed.Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.CONCLUSIONSOur study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.
Background Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes. Methods and findings The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed. Conclusions Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.
Audience Academic
Author Dehghan, Abbas
Tzoulaki, Ioanna
Drenos, Fotios
Elliott, Paul
Tsilidis, Kostas
Dib, Marie-Joe
Gill, Dipender
Zagkos, Loukas
Pinto, Rui
Markozannes, Georgios
Zuber, Verena
Koskeridis, Fotios
AuthorAffiliation 3 Chief Scientific Advisor Office, Research and Early Development, Novo Nordisk, Copenhagen, Denmark
1 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
5 Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
8 BHF Centre of Excellence at Imperial College London, London, United Kingdom
Chinese University of Hong Kong, CHINA
2 UK Dementia Research Institute, Imperial College London, London, United Kingdom
7 Institute of Cardiovascular Sciences, University College London, London, United Kingdom
4 Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom
6 Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, United Kingdom
AuthorAffiliation_xml – name: 4 Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom
– name: 3 Chief Scientific Advisor Office, Research and Early Development, Novo Nordisk, Copenhagen, Denmark
– name: 6 Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, United Kingdom
– name: 8 BHF Centre of Excellence at Imperial College London, London, United Kingdom
– name: Chinese University of Hong Kong, CHINA
– name: 5 Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
– name: 7 Institute of Cardiovascular Sciences, University College London, London, United Kingdom
– name: 1 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
– name: 2 UK Dementia Research Institute, Imperial College London, London, United Kingdom
Author_xml – sequence: 1
  givenname: Loukas
  orcidid: 0000-0002-7700-8102
  surname: Zagkos
  fullname: Zagkos, Loukas
– sequence: 2
  givenname: Marie-Joe
  orcidid: 0000-0001-7591-5684
  surname: Dib
  fullname: Dib, Marie-Joe
– sequence: 3
  givenname: Rui
  orcidid: 0000-0002-8527-4873
  surname: Pinto
  fullname: Pinto, Rui
– sequence: 4
  givenname: Dipender
  orcidid: 0000-0001-7312-7078
  surname: Gill
  fullname: Gill, Dipender
– sequence: 5
  givenname: Fotios
  orcidid: 0000-0002-1253-7556
  surname: Koskeridis
  fullname: Koskeridis, Fotios
– sequence: 6
  givenname: Fotios
  orcidid: 0000-0003-2469-5516
  surname: Drenos
  fullname: Drenos, Fotios
– sequence: 7
  givenname: Georgios
  orcidid: 0000-0001-8481-579X
  surname: Markozannes
  fullname: Markozannes, Georgios
– sequence: 8
  givenname: Paul
  orcidid: 0000-0002-7511-5684
  surname: Elliott
  fullname: Elliott, Paul
– sequence: 9
  givenname: Verena
  surname: Zuber
  fullname: Zuber, Verena
– sequence: 10
  givenname: Kostas
  surname: Tsilidis
  fullname: Tsilidis, Kostas
– sequence: 11
  givenname: Abbas
  orcidid: 0000-0001-6403-016X
  surname: Dehghan
  fullname: Dehghan, Abbas
– sequence: 12
  givenname: Ioanna
  orcidid: 0000-0002-4275-9328
  surname: Tzoulaki
  fullname: Tzoulaki, Ioanna
BackLink https://www.ncbi.nlm.nih.gov/pubmed/36580444$$D View this record in MEDLINE/PubMed
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Cites_doi 10.5539/gjhs.v8n7p18
10.1016/j.ejphar.2011.05.085
10.1186/s12933-018-0740-x
10.1016/j.clnu.2022.02.022
10.1093/hmg/ddy271
10.1161/CIRCULATIONAHA.118.038908
10.1038/s41467-019-13870-3
10.1038/ng.2982
10.1038/s41586-018-0579-z
10.1038/s41588-018-0099-7
10.2337/db10-0502
10.1038/ejcn.2013.197
10.3390/nu11112599
10.1161/CIRCGENETICS.113.000208
10.1111/j.1440-1746.2012.07227.x
10.1038/ncomms11122
10.1136/eb-2012-100960
10.7554/eLife.34408
10.1371/journal.pgen.1002193
10.1038/ng.2897
10.1093/ije/dyv080
10.7326/0003-4819-141-7-200410050-00007
10.1093/ije/dyy262
10.4103/2279-042X.162356
10.1371/journal.pmed.1001779
10.1136/heartjnl-2020-316780
10.1111/j.2517-6161.1995.tb02031.x
10.1016/j.plefa.2014.11.007
10.3945/an.114.006940
10.1161/CIRCGENETICS.112.964619
10.1093/bioinformatics/btu197
10.1016/j.clnesp.2021.04.023
10.1016/j.mayocp.2016.10.018
10.1158/1538-7445.AM2015-3723
10.1038/ng.2802
10.1002/gepi.21965
10.1001/2012.jama.11374
10.1093/aje/kwv017
10.1038/ng.3396
10.1186/s12916-022-02399-w
10.1038/ng.3211
10.1002/hep.1840160418
10.1002/gepi.21758
ContentType Journal Article
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License Copyright: © 2022 Zagkos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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I have read the journal’s policy and the authors of this manuscript have the following competing interests: DG is employed part-time by Novo Nordisk. VZ is a paid statistical consultant on PLOS Medicine’s statistical board.
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References C. von Schacky (pmed.1004141.ref006) 2013; 18
DD Alexander (pmed.1004141.ref007) 2017; 92
Team RC. (pmed.1004141.ref034) 2020
pmed.1004141.ref037
V Zuber (pmed.1004141.ref032) 2020; 11
KL Fritsche (pmed.1004141.ref002) 2015; 6
EC Rizos (pmed.1004141.ref050) 2012; 308
TJ Brown (pmed.1004141.ref046) 2019; 366
WH Guan (pmed.1004141.ref012) 2014; 7
SNB Purcell (pmed.1004141.ref019) 2007
M Nikpay (pmed.1004141.ref022) 2015; 47
EC Rizos (pmed.1004141.ref004) 2021; 107
NL Tintle (pmed.1004141.ref015) 2015; 94
AC Skulas-Ray (pmed.1004141.ref045) 2019; 140
B Gray (pmed.1004141.ref042) 2013; 67
J Bowden (pmed.1004141.ref029) 2016; 40
CT Black LI (pmed.1004141.ref009) 2015; 10
FM Delpino (pmed.1004141.ref043) 2021; 44
CJ Tsai (pmed.1004141.ref039) 2004; 141
PC Calder (pmed.1004141.ref003) 2011; 668
L Yengo (pmed.1004141.ref021) 2018; 27
Y Benjamini (pmed.1004141.ref026) 1995; 57
EM Agency (pmed.1004141.ref044) 2019
N Soranzo (pmed.1004141.ref024) 2010; 59
JK Kim (pmed.1004141.ref041) 2012; 27
RJ Carroll (pmed.1004141.ref035) 2014; 30
C Sudlow (pmed.1004141.ref016) 2015; 12
J Kettunen (pmed.1004141.ref020) 2016; 7
E Sanderson (pmed.1004141.ref033) 2019; 48
S Burgess (pmed.1004141.ref027) 2013; 37
JH Wu (pmed.1004141.ref013) 2013; 6
F Berr (pmed.1004141.ref040) 1992; 16
M Marklund (pmed.1004141.ref052) 2019; 139
JC Lambert (pmed.1004141.ref023) 2013; 45
MC Borges (pmed.1004141.ref051) 2022; 20
S Burgess (pmed.1004141.ref031) 2015; 181
Schizophrenia Working Group of the Psychiatric Genomics C (pmed.1004141.ref038) 2015; 47
E Rajaei (pmed.1004141.ref048) 2015; 8
A Mahajan (pmed.1004141.ref025) 2014; 46
RN Lemaitre (pmed.1004141.ref011) 2011; 7
J Bowden (pmed.1004141.ref028) 2015; 44
G Markozannes (pmed.1004141.ref005) 2022; 41
TC Clarke (pmed.1004141.ref010) 2015; 75
B Elsworth (pmed.1004141.ref018) 2020
K Nagy (pmed.1004141.ref001) 2017
LL O’Mahoney (pmed.1004141.ref008) 2018; 17
L Hooper (pmed.1004141.ref053) 2018
G Hemani (pmed.1004141.ref036) 2018; 7
C Bycroft (pmed.1004141.ref017) 2018; 562
SY Shin (pmed.1004141.ref014) 2014; 46
A Sekikawa (pmed.1004141.ref049) 2019; 11
M Verbanck (pmed.1004141.ref030) 2018; 50
AE Naini (pmed.1004141.ref047) 2015; 4
References_xml – volume: 8
  start-page: 18
  issue: 7
  year: 2015
  ident: pmed.1004141.ref048
  article-title: The Effect of Omega-3 Fatty Acids in Patients With Active Rheumatoid Arthritis Receiving DMARDs Therapy: Double-Blind Randomized Controlled Trial
  publication-title: Global J Health Sci
  doi: 10.5539/gjhs.v8n7p18
– ident: pmed.1004141.ref037
– volume: 668
  start-page: S50
  issue: Suppl 1
  year: 2011
  ident: pmed.1004141.ref003
  article-title: Fatty acids and inflammation: the cutting edge between food and pharma
  publication-title: Eur J Pharmacol
  doi: 10.1016/j.ejphar.2011.05.085
– volume: 17
  start-page: 98
  issue: 1
  year: 2018
  ident: pmed.1004141.ref008
  article-title: Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials
  publication-title: Cardiovasc Diabetol
  doi: 10.1186/s12933-018-0740-x
– volume: 41
  start-page: 923
  issue: 4
  year: 2022
  ident: pmed.1004141.ref005
  article-title: Dose-related meta-analysis for Omega-3 fatty acids supplementation on major adverse cardiovascular events.
  publication-title: Clin Nutr.
  doi: 10.1016/j.clnu.2022.02.022
– volume: 27
  start-page: 3641
  issue: 20
  year: 2018
  ident: pmed.1004141.ref021
  article-title: Meta-analysis of genome-wide association studies for height and body mass index in approximately 700000 individuals of European ancestry
  publication-title: Hum Mol Genet
  doi: 10.1093/hmg/ddy271
– volume: 139
  start-page: 2422
  issue: 21
  year: 2019
  ident: pmed.1004141.ref052
  article-title: Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies.
  publication-title: Circulation
  doi: 10.1161/CIRCULATIONAHA.118.038908
– volume: 11
  start-page: 29
  issue: 1
  year: 2020
  ident: pmed.1004141.ref032
  article-title: Selecting likely causal risk factors from high-throughput experiments using multivariable Mendelian randomization.
  publication-title: Nat Commun.
  doi: 10.1038/s41467-019-13870-3
– year: 2019
  ident: pmed.1004141.ref044
  publication-title: EMA confirms omega-3 fatty acid medicines are not effective in preventing further heart problems after a heart attack.
– volume: 46
  start-page: 543
  issue: 6
  year: 2014
  ident: pmed.1004141.ref014
  article-title: An atlas of genetic influences on human blood metabolites
  publication-title: Nat Genet
  doi: 10.1038/ng.2982
– volume: 562
  start-page: 203
  issue: 7726
  year: 2018
  ident: pmed.1004141.ref017
  article-title: The UK Biobank resource with deep phenotyping and genomic data
  publication-title: Nature
  doi: 10.1038/s41586-018-0579-z
– volume: 50
  start-page: 693
  issue: 5
  year: 2018
  ident: pmed.1004141.ref030
  article-title: Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases
  publication-title: Nat Genet
  doi: 10.1038/s41588-018-0099-7
– volume: 59
  start-page: 3229
  issue: 12
  year: 2010
  ident: pmed.1004141.ref024
  article-title: Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways.
  publication-title: Diabetes
  doi: 10.2337/db10-0502
– volume: 67
  start-page: 1234
  issue: 12
  year: 2013
  ident: pmed.1004141.ref042
  article-title: Omega-3 fatty acids: a review of the effects on adiponectin and leptin and potential implications for obesity management.
  publication-title: Eur J Clin Nutr
  doi: 10.1038/ejcn.2013.197
– volume: 11
  issue: 11
  year: 2019
  ident: pmed.1004141.ref049
  article-title: Effect of High-Dose Marine Omega-3 Fatty Acids on Atherosclerosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
  publication-title: Nutrients
  doi: 10.3390/nu11112599
– volume: 7
  start-page: 321
  issue: 3
  year: 2014
  ident: pmed.1004141.ref012
  article-title: Genome-Wide Association Study of Plasma N6 Polyunsaturated Fatty Acids Within the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.
  publication-title: Circ-Cardiovasc Gene
  doi: 10.1161/CIRCGENETICS.113.000208
– volume: 27
  start-page: 1745
  issue: 11
  year: 2012
  ident: pmed.1004141.ref041
  article-title: N-3 polyunsaturated fatty acid attenuates cholesterol gallstones by suppressing mucin production with a high cholesterol diet in mice
  publication-title: J Gastroenterol Hepatol
  doi: 10.1111/j.1440-1746.2012.07227.x
– volume: 7
  start-page: 11122
  year: 2016
  ident: pmed.1004141.ref020
  article-title: Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA.
  publication-title: Nat Commun.
  doi: 10.1038/ncomms11122
– volume: 18
  start-page: e33
  issue: 4
  year: 2013
  ident: pmed.1004141.ref006
  article-title: Meta-analysing randomised controlled trials with omega-3 fatty acids in cardiovascular disease.
  publication-title: Evid Based Med
  doi: 10.1136/eb-2012-100960
– volume: 7
  year: 2018
  ident: pmed.1004141.ref036
  article-title: The MR-Base platform supports systematic causal inference across the human phenome.
  publication-title: Elife
  doi: 10.7554/eLife.34408
– volume: 7
  start-page: e1002193
  issue: 7
  year: 2011
  ident: pmed.1004141.ref011
  article-title: Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.
  publication-title: PLoS Genet.
  doi: 10.1371/journal.pgen.1002193
– volume: 46
  start-page: 234
  issue: 3
  year: 2014
  ident: pmed.1004141.ref025
  article-title: Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
  publication-title: Nat Genet
  doi: 10.1038/ng.2897
– volume: 44
  start-page: 512
  issue: 2
  year: 2015
  ident: pmed.1004141.ref028
  article-title: Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression.
  publication-title: Int J Epidemiol
  doi: 10.1093/ije/dyv080
– volume-title: R: A language and environment for statistical computing
  year: 2020
  ident: pmed.1004141.ref034
– volume: 141
  start-page: 514
  issue: 7
  year: 2004
  ident: pmed.1004141.ref039
  article-title: The effect of long-term intake of cis unsaturated fats on the risk for gallstone disease in men—A prospective cohort study
  publication-title: Ann Intern Med
  doi: 10.7326/0003-4819-141-7-200410050-00007
– volume: 48
  start-page: 713
  issue: 3
  year: 2019
  ident: pmed.1004141.ref033
  article-title: An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings.
  publication-title: Int J Epidemiol
  doi: 10.1093/ije/dyy262
– volume: 4
  start-page: 135
  issue: 3
  year: 2015
  ident: pmed.1004141.ref047
  article-title: Effect of Omega-3 fatty acids on blood pressure and serum lipids in continuous ambulatory peritoneal dialysis patients
  publication-title: J Res Pharm Pract
  doi: 10.4103/2279-042X.162356
– volume: 12
  start-page: e1001779
  issue: 3
  year: 2015
  ident: pmed.1004141.ref016
  article-title: UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age.
  publication-title: PLoS Med.
  doi: 10.1371/journal.pmed.1001779
– year: 2017
  ident: pmed.1004141.ref001
  publication-title: Importance of Fatty Acids in Physiopathology of Human Body
– volume: 107
  start-page: 150
  issue: 2
  year: 2021
  ident: pmed.1004141.ref004
  article-title: Omega-3 supplementation and cardiovascular disease: formulation-based systematic review and meta-analysis with trial sequential analysis
  publication-title: Heart
  doi: 10.1136/heartjnl-2020-316780
– volume: 57
  start-page: 289
  issue: 1
  year: 1995
  ident: pmed.1004141.ref026
  article-title: Controlling the False Discovery Rate—a Practical and Powerful Approach to Multiple Testing.
  publication-title: J R Stat Soc B
  doi: 10.1111/j.2517-6161.1995.tb02031.x
– volume: 366
  year: 2019
  ident: pmed.1004141.ref046
  article-title: Omega-3, omega-6, and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review and meta-analysis of randomised controlled trials
  publication-title: Bmj-Brit Med J
– volume: 140
  start-page: E673
  issue: 12
  year: 2019
  ident: pmed.1004141.ref045
  article-title: Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association
  publication-title: Circulation
– volume: 94
  start-page: 65
  year: 2015
  ident: pmed.1004141.ref015
  article-title: A genome-wide association study of saturated, mono- and polyunsaturated red blood cell fatty acids in the Framingham Heart Offspring Study
  publication-title: Prostaglandins Leukot Essent Fatty Acids
  doi: 10.1016/j.plefa.2014.11.007
– volume: 6
  start-page: 293S
  issue: 3
  year: 2015
  ident: pmed.1004141.ref002
  article-title: The science of fatty acids and inflammation
  publication-title: Adv Nutr
  doi: 10.3945/an.114.006940
– volume: 6
  start-page: 171
  issue: 2
  year: 2013
  ident: pmed.1004141.ref013
  article-title: Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.
  publication-title: Circ Cardiovasc Genet.
  doi: 10.1161/CIRCGENETICS.112.964619
– year: 2007
  ident: pmed.1004141.ref019
  article-title: PLINK: a toolset for whole-genome association and population-based linkage analysis
  publication-title: Am J Hum Genet
– issue: 11
  year: 2018
  ident: pmed.1004141.ref053
  article-title: Omega-6 fats for the primary and secondary prevention of cardiovascular disease.
  publication-title: Cochrane Db Syst Rev.
– volume: 30
  start-page: 2375
  issue: 16
  year: 2014
  ident: pmed.1004141.ref035
  article-title: R PheWAS: data analysis and plotting tools for phenome-wide association studies in the R environment
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btu197
– volume: 44
  start-page: 122
  year: 2021
  ident: pmed.1004141.ref043
  article-title: Effects of omega-3 supplementation on body weight and body fat mass: A systematic review.
  publication-title: Clinical Nutrition Espen
  doi: 10.1016/j.clnesp.2021.04.023
– volume: 92
  start-page: 15
  issue: 1
  year: 2017
  ident: pmed.1004141.ref007
  article-title: A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk
  publication-title: Mayo Clin Proc
  doi: 10.1016/j.mayocp.2016.10.018
– volume: 75
  year: 2015
  ident: pmed.1004141.ref010
  article-title: The use of complementary health approaches among US cancer survivors
  publication-title: Cancer Res
  doi: 10.1158/1538-7445.AM2015-3723
– volume: 45
  start-page: 1452
  issue: 12
  year: 2013
  ident: pmed.1004141.ref023
  article-title: Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease
  publication-title: Nat Genet
  doi: 10.1038/ng.2802
– volume: 40
  start-page: 304
  issue: 4
  year: 2016
  ident: pmed.1004141.ref029
  article-title: Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator
  publication-title: Genet Epidemiol
  doi: 10.1002/gepi.21965
– volume: 308
  start-page: 1024
  issue: 10
  year: 2012
  ident: pmed.1004141.ref050
  article-title: Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis
  publication-title: JAMA
  doi: 10.1001/2012.jama.11374
– volume: 181
  start-page: 290
  issue: 4
  year: 2015
  ident: pmed.1004141.ref031
  article-title: Multivariable Mendelian Randomization: The Use of Pleiotropic Genetic Variants to Estimate Causal Effects
  publication-title: Am J Epidemiol
  doi: 10.1093/aje/kwv017
– year: 2020
  ident: pmed.1004141.ref018
  article-title: The MRC IEU OpenGWAS data infrastructure.
  publication-title: BioRxiv [preprint].
– volume: 47
  start-page: 1121
  issue: 10
  year: 2015
  ident: pmed.1004141.ref022
  article-title: A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease
  publication-title: Nat Genet
  doi: 10.1038/ng.3396
– volume: 20
  issue: 1
  year: 2022
  ident: pmed.1004141.ref051
  article-title: 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.
  publication-title: BMC Med.
  doi: 10.1186/s12916-022-02399-w
– volume: 47
  start-page: 291
  issue: 3
  year: 2015
  ident: pmed.1004141.ref038
  article-title: LD Score regression distinguishes confounding from polygenicity in genome-wide association studies
  publication-title: Nat Genet
  doi: 10.1038/ng.3211
– volume: 16
  start-page: 960
  issue: 4
  year: 1992
  ident: pmed.1004141.ref040
  article-title: Dietary N-3 Polyunsaturated Fatty-Acids Decrease Biliary Cholesterol Saturation in Gallstone Disease
  publication-title: Hepatology
  doi: 10.1002/hep.1840160418
– volume: 37
  start-page: 658
  issue: 7
  year: 2013
  ident: pmed.1004141.ref027
  article-title: Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data
  publication-title: Genet Epidemiol
  doi: 10.1002/gepi.21758
– volume: 10
  start-page: 1
  issue: 78
  year: 2015
  ident: pmed.1004141.ref009
  article-title: Use of complementary health approaches among children aged 4–17 years in the United States: National Health Interview Survey.
  publication-title: Natl Health Stat Rep.
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Snippet Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies...
Background Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from...
Loukas Zagkos and colleagues conduct Mendelian randomisation analysis to investigate potential causal associations of circulating fatty acids and 845 disease...
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StartPage e1004141
SubjectTerms Adult
Aged
Analysis
Bayes Theorem
Biology and Life Sciences
Cholecystitis - epidemiology
Cholecystitis - genetics
Cholelithiasis - epidemiology
Cholelithiasis - genetics
Coronary Disease - epidemiology
Coronary Disease - genetics
Coronary heart disease
Docosahexaenoic Acids - blood
Docosahexaenoic Acids - genetics
Epidemiology
Fatty Acids, Omega-3 - blood
Fatty Acids, Omega-3 - genetics
Fatty Acids, Omega-6 - blood
Fatty Acids, Omega-6 - genetics
Female
Gallstones
Genetic aspects
Genetic Predisposition to Disease
Genetics
Health aspects
Humans
Male
Medical research
Medicine and Health Sciences
Medicine, Experimental
Mendelian Randomization Analysis - methods
Middle Aged
Obesity
Obesity - epidemiology
Obesity - genetics
Omega-3 fatty acids
Prevention
Risk factors
Unsaturated fatty acids
Title Associations of genetically predicted fatty acid levels across the phenome: A mendelian randomisation study
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https://pubmed.ncbi.nlm.nih.gov/PMC9799317
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