Mendelian randomization of blood lipids for coronary heart disease

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Holmes, Michael V. (author)

Mendelian randomization of blood lipids for coronary heart disease

Article/chapterEnglish2015

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2014-01-28
Oxford University Press (OUP),2015
electronicrdacarrier

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LIBRIS-ID:oai:lup.lub.lu.se:0a984a07-185b-496a-b980-e64a0bc4a3e2
https://lup.lub.lu.se/record/5281446URI
https://doi.org/10.1093/eurheartj/eht571DOI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

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Aims To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. Methods and results We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a priormeta-analysis (threshold P < 2 x 10(-6)); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P <= 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestrictedallele score (48SNPs) was associated with CHD(OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). Conclusion The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kardiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cardiac and Cardiovascular Systems hsv//eng
Lipids
Heart disease
Mendelian randomization
Aetiology
Epidemiology

Added entries (persons, corporate bodies, meetings, titles ...)

Asselbergs, Folkert W. (author)
Palmer, Tom M. (author)
Drenos, Fotios (author)
Lanktree, Matthew B. (author)
Nelson, Christopher P. (author)
Dale, Caroline E. (author)
Padmanabhan, Sandosh (author)
Finan, Chris (author)
Swerdlow, Daniel I. (author)
Tragante, Vinicius (author)
van Iperen, Erik P. A. (author)
Sivapalaratnam, Suthesh (author)
Shah, Sonia (author)
Elbers, Clara C. (author)
Shah, Tina (author)
Engmann, Jorgen (author)
Giambartolomei, Claudia (author)
White, Jon (author)
Zabaneh, Delilah (author)
Sofat, Reecha (author)
McLachlan, Stela (author)
Doevendans, Pieter A. (author)
Balmforth, Anthony J. (author)
Hall, Alistair S. (author)
North, Kari E. (author)
Almoguera, Berta (author)
Hoogeveen, Ron C. (author)
Cushman, Mary (author)
Fornage, Myriam (author)
Patel, Sanjay R. (author)
Redline, Susan (author)
Siscovick, David S. (author)
Tsai, Michael Y. (author)
Karczewski, Konrad J. (author)
Hofker, Marten H. (author)
Verschuren, W. Monique (author)
Bots, Michiel L. (author)
van der Schouw, Yvonne T. (author)
Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome (author)
Dominiczak, Anna F. (author)
Morris, Richard (author)
Ben-Shlomo, Yoav (author)
Price, Jackie (author)
Kumari, Meena (author)
Baumert, Jens (author)
Peters, Annette (author)
Thorand, Barbara (author)
Koenig, Wolfgang (author)
Gaunt, Tom R. (author)
Humphries, Steve E. (author)
Clarke, Robert (author)
Watkins, Hugh (author)
Farrall, Martin (author)
Wilson, James G. (author)
Rich, Stephen S. (author)
de Bakker, Paul I. W. (author)
Lange, Leslie A. (author)
Smith, George Davey (author)
Reiner, Alex P. (author)
Talmud, Philippa J. (author)
Kivimaeki, Mika (author)
Lawlor, Debbie A. (author)
Dudbridge, Frank (author)
Samani, Nilesh J. (author)
Keating, Brendan J. (author)
Hingorani, Aroon D. (author)
Casas, Juan P. (author)
Kardiovaskulär forskning - hypertoniForskargrupper vid Lunds universitet (creator_code:org_t)

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In:European Heart Journal: Oxford University Press (OUP)36:9, s. 539-5391522-96450195-668X

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By the author/editor: Holmes, Michael ...; Asselbergs, Folk ...; Palmer, Tom M.; Drenos, Fotios; Lanktree, Matthe ...; Nelson, Christop ...; show more...; Dale, Caroline E ...; Padmanabhan, San ...; Finan, Chris; Swerdlow, Daniel ...; Tragante, Vinici ...; van Iperen, Erik ...; Sivapalaratnam, ...; Shah, Sonia; Elbers, Clara C.; Shah, Tina; Engmann, Jorgen; Giambartolomei, ...; White, Jon; Zabaneh, Delilah; Sofat, Reecha; McLachlan, Stela; Doevendans, Piet ...; Balmforth, Antho ...; Hall, Alistair S ...; North, Kari E.; Almoguera, Berta; Hoogeveen, Ron C ...; Cushman, Mary; Fornage, Myriam; Patel, Sanjay R.; Redline, Susan; Siscovick, David ...; Tsai, Michael Y.; Karczewski, Konr ...; Hofker, Marten H ...; Verschuren, W. M ...; Bots, Michiel L.; van der Schouw, ...; Melander, Olle; Dominiczak, Anna ...; Morris, Richard; Ben-Shlomo, Yoav; Price, Jackie; Kumari, Meena; Baumert, Jens; Peters, Annette; Thorand, Barbara; Koenig, Wolfgang; Gaunt, Tom R.; Humphries, Steve ...; Clarke, Robert; Watkins, Hugh; Farrall, Martin; Wilson, James G.; Rich, Stephen S.; de Bakker, Paul ...; Lange, Leslie A.; Smith, George Da ...; Reiner, Alex P.; Talmud, Philippa ...; Kivimaeki, Mika; Lawlor, Debbie A ...; Dudbridge, Frank; Samani, Nilesh J ...; Keating, Brendan ...; Hingorani, Aroon ...; Casas, Juan P.; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

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