Discovery and refinement of loci associated with lipid levels

Global Lipids Genetics Consortium

doi:10.1038/ng.2797

Discovery and refinement of loci associated with lipid levels

Global Lipids Genetics Consortium

Research output: Contribution to journal › Article › peer-review

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Abstract

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P <5 × 10 ^-8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

Original language	English
Pages (from-to)	1274-1283
Number of pages	10
Journal	Nature Genetics
Volume	45
Issue number	11
DOIs	https://doi.org/10.1038/ng.2797
Publication status	Published - 2013

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@article{cab7971191374d7ca0e5dda8a938c696,

title = "Discovery and refinement of loci associated with lipid levels",

abstract = "Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P <5 × 10 -8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.",

author = "Willer, {Cristen J.} and Schmidt, {Ellen M.} and Peloso, {Gina M.} and Stefan Gustafsson and Stavroula Kanoni and Andrea Ganna and Jin Chen and M.L. Buchkovich and S. Mora and J.S. Beckmann and J.L. Bragg-Gresham and H.-Y. Chang and A. Demirkan and {Den Hertog}, H.M. and R. Do and Donnelly, {Louise A.} and G.B. Ehret and T. Esko and M.F. Feitosa and T. Ferreira and K. Fischer and P. Fontanillas and R.M. Fraser and D.F. Freitag and D. Gurdasani and K. Heikkil{\"a} and E. Hypp{\"o}nen and A. Isaacs and A.U. Jackson and {\AA}. Johansson and T. Johnson and M. Kaakinen and J. Kettunen and M.E. Kleber and X. Li and J. Luan and L.-P. Lyytik{\"a}inen and P.K.E. Magnusson and M. Mangino and E. Mihailov and M.E. Montasser and M. M{\"u}ller-Nurasyid and I.M. Nolte and J.R. O'Connell and M. Perola and A.-K. Petersen and S. Sanna and Doney, {Alex. S. F.} and Morris, {Andrew D.} and Palmer, {Colin N. A.} and {Global Lipids Genetics Consortium}",

year = "2013",

doi = "10.1038/ng.2797",

language = "English",

volume = "45",

pages = "1274--1283",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "11",

}

TY - JOUR

T1 - Discovery and refinement of loci associated with lipid levels

AU - Willer, Cristen J.

AU - Schmidt, Ellen M.

AU - Peloso, Gina M.

AU - Gustafsson, Stefan

AU - Kanoni, Stavroula

AU - Ganna, Andrea

AU - Chen, Jin

AU - Buchkovich, M.L.

AU - Mora, S.

AU - Beckmann, J.S.

AU - Bragg-Gresham, J.L.

AU - Chang, H.-Y.

AU - Demirkan, A.

AU - Den Hertog, H.M.

AU - Do, R.

AU - Donnelly, Louise A.

AU - Ehret, G.B.

AU - Esko, T.

AU - Feitosa, M.F.

AU - Ferreira, T.

AU - Fischer, K.

AU - Fontanillas, P.

AU - Fraser, R.M.

AU - Freitag, D.F.

AU - Gurdasani, D.

AU - Heikkilä, K.

AU - Hyppönen, E.

AU - Isaacs, A.

AU - Jackson, A.U.

AU - Johansson, Å.

AU - Johnson, T.

AU - Kaakinen, M.

AU - Kettunen, J.

AU - Kleber, M.E.

AU - Li, X.

AU - Luan, J.

AU - Lyytikäinen, L.-P.

AU - Magnusson, P.K.E.

AU - Mangino, M.

AU - Mihailov, E.

AU - Montasser, M.E.

AU - Müller-Nurasyid, M.

AU - Nolte, I.M.

AU - O'Connell, J.R.

AU - Perola, M.

AU - Petersen, A.-K.

AU - Sanna, S.

AU - Doney, Alex. S. F.

AU - Morris, Andrew D.

AU - Palmer, Colin N. A.

AU - Global Lipids Genetics Consortium

PY - 2013

Y1 - 2013

N2 - Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P <5 × 10 -8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

AB - Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P <5 × 10 -8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

UR - http://www.scopus.com/inward/record.url?scp=84887099827&partnerID=8YFLogxK

U2 - 10.1038/ng.2797

DO - 10.1038/ng.2797

M3 - Article

C2 - 24097068

AN - SCOPUS:84887099827

SN - 1061-4036

VL - 45

SP - 1274

EP - 1283

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Discovery and refinement of loci associated with lipid levels

Abstract

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