Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions.
Previous Mendelian randomization studies have suggested that, while low-density lipoprotein cholesterol (LDL-c) and triglycerides are causally implicated in coronary artery disease (CAD) risk, high-density lipoprotein cholesterol (HDL-c) may not be, with causal effect estimates compatible with the n...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4193746?pdf=render |
| _version_ | 1818008962557018112 |
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| author | Stephen Burgess Daniel F Freitag Hassan Khan Donal N Gorman Simon G Thompson |
| author_facet | Stephen Burgess Daniel F Freitag Hassan Khan Donal N Gorman Simon G Thompson |
| author_sort | Stephen Burgess |
| collection | DOAJ |
| description | Previous Mendelian randomization studies have suggested that, while low-density lipoprotein cholesterol (LDL-c) and triglycerides are causally implicated in coronary artery disease (CAD) risk, high-density lipoprotein cholesterol (HDL-c) may not be, with causal effect estimates compatible with the null.The causal effects of these three lipid fractions can be better identified using the extended methods of 'multivariable Mendelian randomization'. We employ this approach using published data on 185 lipid-related genetic variants and their associations with lipid fractions in 188,578 participants, and with CAD risk in 22,233 cases and 64,762 controls. Our results suggest that HDL-c may be causally protective of CAD risk, independently of the effects of LDL-c and triglycerides. Estimated causal odds ratios per standard deviation increase, based on 162 variants not having pleiotropic associations with either blood pressure or body mass index, are 1.57 (95% credible interval 1.45 to 1.70) for LDL-c, 0.91 (0.83 to 0.99, p-value = 0.028) for HDL-c, and 1.29 (1.16 to 1.43) for triglycerides.Some interventions on HDL-c concentrations may influence risk of CAD, but to a lesser extent than interventions on LDL-c. A causal interpretation of these estimates relies on the assumption that the genetic variants do not have pleiotropic associations with risk factors on other pathways to CAD. If they do, a weaker conclusion is that genetic predictors of LDL-c, HDL-c and triglycerides each have independent associations with CAD risk. |
| first_indexed | 2024-04-14T05:35:56Z |
| format | Article |
| id | doaj.art-c2ddc3ccf66342feb014645955a5f964 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T05:35:56Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c2ddc3ccf66342feb014645955a5f9642022-12-22T02:09:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e10889110.1371/journal.pone.0108891Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions.Stephen BurgessDaniel F FreitagHassan KhanDonal N GormanSimon G ThompsonPrevious Mendelian randomization studies have suggested that, while low-density lipoprotein cholesterol (LDL-c) and triglycerides are causally implicated in coronary artery disease (CAD) risk, high-density lipoprotein cholesterol (HDL-c) may not be, with causal effect estimates compatible with the null.The causal effects of these three lipid fractions can be better identified using the extended methods of 'multivariable Mendelian randomization'. We employ this approach using published data on 185 lipid-related genetic variants and their associations with lipid fractions in 188,578 participants, and with CAD risk in 22,233 cases and 64,762 controls. Our results suggest that HDL-c may be causally protective of CAD risk, independently of the effects of LDL-c and triglycerides. Estimated causal odds ratios per standard deviation increase, based on 162 variants not having pleiotropic associations with either blood pressure or body mass index, are 1.57 (95% credible interval 1.45 to 1.70) for LDL-c, 0.91 (0.83 to 0.99, p-value = 0.028) for HDL-c, and 1.29 (1.16 to 1.43) for triglycerides.Some interventions on HDL-c concentrations may influence risk of CAD, but to a lesser extent than interventions on LDL-c. A causal interpretation of these estimates relies on the assumption that the genetic variants do not have pleiotropic associations with risk factors on other pathways to CAD. If they do, a weaker conclusion is that genetic predictors of LDL-c, HDL-c and triglycerides each have independent associations with CAD risk.http://europepmc.org/articles/PMC4193746?pdf=render |
| spellingShingle | Stephen Burgess Daniel F Freitag Hassan Khan Donal N Gorman Simon G Thompson Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions. PLoS ONE |
| title | Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions. |
| title_full | Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions. |
| title_fullStr | Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions. |
| title_full_unstemmed | Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions. |
| title_short | Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions. |
| title_sort | using multivariable mendelian randomization to disentangle the causal effects of lipid fractions |
| url | http://europepmc.org/articles/PMC4193746?pdf=render |
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