Discovery and refinement of loci associated with lipid levels

Global Lipids Genetics Consortium; Cristen J Willer; Ellen M Schmidt; Sebanti Sengupta; Gina M Peloso; Stefan Gustafsson; Stavroula Kanoni; Andrea Ganna; Jin Chen; Martin L Buchkovich; Samia Mora; Jacques S Beckmann; Jennifer L Bragg-Gresham; Hsing-Yi Chang; Ayşe Demirkan; Heleen M Den Hertog; Ron Do; Louise A Donnelly; Georg B Ehret; Tõnu Esko; Mary F Feitosa; Teresa Ferreira; Krista Fischer; Pierre Fontanillas; Ross M Fraser; Daniel F Freitag; Deepti Gurdasani; Kauko Heikkilä; Elina Hyppönen; Aaron Isaacs; Anne U Jackson; Asa Johansson; Toby Johnson; Marika Kaakinen; Johannes Kettunen; Marcus E Kleber; Xiaohui Li; Jian'an Luan; Leo-Pekka Lyytikäinen; Patrik K E Magnusson; Massimo Mangino; Evelin Mihailov; May E Montasser; Jennifer L Bolton; Caroline Hayward; Igor Rudan; Sarah H Wild; James F Wilson; Harry Campbell; Andrew Morris; Jackie F Price

doi:10.1038/ng.2797

Discovery and refinement of loci associated with lipid levels

Global Lipids Genetics Consortium, Cristen J Willer, Ellen M Schmidt, Sebanti Sengupta, Gina M Peloso, Stefan Gustafsson, Stavroula Kanoni, Andrea Ganna, Jin Chen, Martin L Buchkovich, Samia Mora, Jacques S Beckmann, Jennifer L Bragg-Gresham, Hsing-Yi Chang, Ayşe Demirkan, Heleen M Den Hertog, Ron Do, Louise A Donnelly, Georg B Ehret, Tõnu EskoMary F Feitosa, Teresa Ferreira, Krista Fischer, Pierre Fontanillas, Ross M Fraser, Daniel F Freitag, Deepti Gurdasani, Kauko Heikkilä, Elina Hyppönen, Aaron Isaacs, Anne U Jackson, Asa Johansson, Toby Johnson, Marika Kaakinen, Johannes Kettunen, Marcus E Kleber, Xiaohui Li, Jian'an Luan, Leo-Pekka Lyytikäinen, Patrik K E Magnusson, Massimo Mangino, Evelin Mihailov, May E Montasser, Jennifer L Bolton, Caroline Hayward, Igor Rudan, Sarah H Wild, James F Wilson, Harry Campbell, Andrew Morris, Jackie F Price

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

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 x 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)	1274-83
Number of pages	10
Journal	Nature Genetics
Volume	45
Issue number	11
DOIs	https://doi.org/10.1038/ng.2797
Publication status	Published - Nov 2013

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10.1038/ng.2797

Discovery and refinement of loci associated with lipid levels.
Published in final edited form as: Nat Genet. Nov 2013; 45(11): 10.1038/ng.2797. Published online Oct 6, 2013. doi: 10.1038/ng.2797
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Global Lipids Genetics Consortium, Willer, C. J., Schmidt, E. M., Sengupta, S., Peloso, G. M., Gustafsson, S., Kanoni, S., Ganna, A., Chen, J., Buchkovich, M. L., Mora, S., Beckmann, J. S., Bragg-Gresham, J. L., Chang, H.-Y., Demirkan, A., Den Hertog, H. M., Do, R., Donnelly, L. A., Ehret, G. B., ... Price, J. F. (2013). Discovery and refinement of loci associated with lipid levels. Nature Genetics, 45(11), 1274-83. https://doi.org/10.1038/ng.2797

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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 x 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 = "\{Global Lipids Genetics Consortium\} and Willer, \{Cristen J\} and Schmidt, \{Ellen M\} and Sebanti Sengupta and Peloso, \{Gina M\} and Stefan Gustafsson and Stavroula Kanoni and Andrea Ganna and Jin Chen and Buchkovich, \{Martin L\} and Samia Mora and Beckmann, \{Jacques S\} and Bragg-Gresham, \{Jennifer L\} and Hsing-Yi Chang and Ay{\c s}e Demirkan and \{Den Hertog\}, \{Heleen M\} and Ron Do and Donnelly, \{Louise A\} and Ehret, \{Georg B\} and T{\~o}nu Esko and Feitosa, \{Mary F\} and Teresa Ferreira and Krista Fischer and Pierre Fontanillas and Fraser, \{Ross M\} and Freitag, \{Daniel F\} and Deepti Gurdasani and Kauko Heikkil{\"a} and Elina Hypp{\"o}nen and Aaron Isaacs and Jackson, \{Anne U\} and Asa Johansson and Toby Johnson and Marika Kaakinen and Johannes Kettunen and Kleber, \{Marcus E\} and Xiaohui Li and Jian'an Luan and Leo-Pekka Lyytik{\"a}inen and Magnusson, \{Patrik K E\} and Massimo Mangino and Evelin Mihailov and Montasser, \{May E\} and Bolton, \{Jennifer L\} and Caroline Hayward and Igor Rudan and Wild, \{Sarah H\} and Wilson, \{James F\} and Harry Campbell and Andrew Morris and Price, \{Jackie F\}",

year = "2013",

month = nov,

doi = "10.1038/ng.2797",

language = "English",

volume = "45",

pages = "1274--83",

journal = "Nature Genetics",

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Global Lipids Genetics Consortium, Willer, CJ, Schmidt, EM, Sengupta, S, Peloso, GM, Gustafsson, S, Kanoni, S, Ganna, A, Chen, J, Buchkovich, ML, Mora, S, Beckmann, JS, Bragg-Gresham, JL, Chang, H-Y, Demirkan, A, Den Hertog, HM, Do, R, Donnelly, LA, Ehret, GB, Esko, T, Feitosa, MF, Ferreira, T, Fischer, K, Fontanillas, P, Fraser, RM, Freitag, DF, Gurdasani, D, Heikkilä, K, Hyppönen, E, Isaacs, A, Jackson, AU, Johansson, A, Johnson, T, Kaakinen, M, Kettunen, J, Kleber, ME, Li, X, Luan, J, Lyytikäinen, L-P, Magnusson, PKE, Mangino, M, Mihailov, E, Montasser, ME, Bolton, JL, Hayward, C , Rudan, I , Wild, SH , Wilson, JF , Campbell, H , Morris, A & Price, JF 2013, 'Discovery and refinement of loci associated with lipid levels', Nature Genetics, vol. 45, no. 11, pp. 1274-83. https://doi.org/10.1038/ng.2797

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AU - Global Lipids Genetics Consortium

AU - Willer, Cristen J

AU - Schmidt, Ellen M

AU - Sengupta, Sebanti

AU - Peloso, Gina M

AU - Gustafsson, Stefan

AU - Kanoni, Stavroula

AU - Ganna, Andrea

AU - Chen, Jin

AU - Buchkovich, Martin L

AU - Mora, Samia

AU - Beckmann, Jacques S

AU - Bragg-Gresham, Jennifer L

AU - Chang, Hsing-Yi

AU - Demirkan, Ayşe

AU - Den Hertog, Heleen M

AU - Do, Ron

AU - Donnelly, Louise A

AU - Ehret, Georg B

AU - Esko, Tõnu

AU - Feitosa, Mary F

AU - Ferreira, Teresa

AU - Fischer, Krista

AU - Fontanillas, Pierre

AU - Fraser, Ross M

AU - Freitag, Daniel F

AU - Gurdasani, Deepti

AU - Heikkilä, Kauko

AU - Hyppönen, Elina

AU - Isaacs, Aaron

AU - Jackson, Anne U

AU - Johansson, Asa

AU - Johnson, Toby

AU - Kaakinen, Marika

AU - Kettunen, Johannes

AU - Kleber, Marcus E

AU - Li, Xiaohui

AU - Luan, Jian'an

AU - Lyytikäinen, Leo-Pekka

AU - Magnusson, Patrik K E

AU - Mangino, Massimo

AU - Mihailov, Evelin

AU - Montasser, May E

AU - Bolton, Jennifer L

AU - Hayward, Caroline

AU - Rudan, Igor

AU - Wild, Sarah H

AU - Wilson, James F

AU - Campbell, Harry

AU - Morris, Andrew

AU - Price, Jackie F

PY - 2013/11

Y1 - 2013/11

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 x 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 x 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.

U2 - 10.1038/ng.2797

DO - 10.1038/ng.2797

M3 - Article

C2 - 24097068

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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