Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts

YS Aulchenko; S Ripatti; I Lindqvist; D Boomsma; IM Heid; PP Pramstaller; BWJH Penninx; Cecile Janssens; JF Wilson; T Spector; NG Martin; NL Pedersen; KO Kyvik; J Kaprio; Bert Hofman; NB Freimer; MR Jarvelin; U Gyllensten; H Campbell; I Rudan; A Johansson; F Marroni; C Hayward; V Vitart; I Jonasson; C Pattaro; A Wright; N Hastie; I Pichler; AA Hicks; M Falchi; G Willemsen; JJ (Jouke Jan) Hottenga; EJC de Geus; GW Montgomery; J Whitfield; P Magnusson; J Saharinen; M Perola; K Silander; Aaron Isaacs; E.J.G. Sijbrands; André Uitterlinden; JCM Witteman; Ben Oostra; P Elliott; A Ruokonen; C Sabatti; C Gieger; T Meitinger; F Kronenberg; A Doring; HE Wichmann; JH Smit; MI McCarthy; Cornelia Duijn; L Peltonen

doi:10.1038/ng.269

Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts

YS Aulchenko, S Ripatti, I Lindqvist, D Boomsma, IM Heid, PP Pramstaller, BWJH Penninx, Cecile Janssens, JF Wilson, T Spector, NG Martin, NL Pedersen, KO Kyvik, J Kaprio, Bert Hofman, NB Freimer, MR Jarvelin, U Gyllensten, H Campbell, I RudanA Johansson, F Marroni, C Hayward, V Vitart, I Jonasson, C Pattaro, A Wright, N Hastie, I Pichler, AA Hicks, M Falchi, G Willemsen, JJ (Jouke Jan) Hottenga, EJC de Geus, GW Montgomery, J Whitfield, P Magnusson, J Saharinen, M Perola, K Silander, Aaron Isaacs, E.J.G. Sijbrands, André Uitterlinden, JCM Witteman, Ben Oostra, P Elliott, A Ruokonen, C Sabatti, C Gieger, T Meitinger, F Kronenberg, A Doring, HE Wichmann, JH Smit, MI McCarthy, Cornelia Duijn, L Peltonen

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

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Abstract

Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.

Original language	Undefined/Unknown
Pages (from-to)	47-55
Number of pages	9
Journal	Nature Genetics
Volume	41
Issue number	1
DOIs	https://doi.org/10.1038/ng.269
Publication status	Published - 2009

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10.1038/ng.269

http://hdl.handle.net/1765/25070

Cite this

Aulchenko, YS., Ripatti, S., Lindqvist, I., Boomsma, D., Heid, IM., Pramstaller, PP., Penninx, BWJH., Janssens, C., Wilson, JF., Spector, T., Martin, NG., Pedersen, NL., Kyvik, KO., Kaprio, J., Hofman, B., Freimer, NB., Jarvelin, MR., Gyllensten, U., Campbell, H., ... Peltonen, L. (2009). Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nature Genetics, 41(1), 47-55. https://doi.org/10.1038/ng.269

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title = "Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts",

abstract = "Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.",

author = "YS Aulchenko and S Ripatti and I Lindqvist and D Boomsma and IM Heid and PP Pramstaller and BWJH Penninx and Cecile Janssens and JF Wilson and T Spector and NG Martin and NL Pedersen and KO Kyvik and J Kaprio and Bert Hofman and NB Freimer and MR Jarvelin and U Gyllensten and H Campbell and I Rudan and A Johansson and F Marroni and C Hayward and V Vitart and I Jonasson and C Pattaro and A Wright and N Hastie and I Pichler and AA Hicks and M Falchi and G Willemsen and Hottenga, {JJ (Jouke Jan)} and {de Geus}, EJC and GW Montgomery and J Whitfield and P Magnusson and J Saharinen and M Perola and K Silander and Aaron Isaacs and E.J.G. Sijbrands and Andr{\'e} Uitterlinden and JCM Witteman and Ben Oostra and P Elliott and A Ruokonen and C Sabatti and C Gieger and T Meitinger and F Kronenberg and A Doring and HE Wichmann and JH Smit and MI McCarthy and Cornelia Duijn and L Peltonen",

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doi = "10.1038/ng.269",

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volume = "41",

pages = "47--55",

journal = "Nature Genetics",

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Aulchenko, YS, Ripatti, S, Lindqvist, I, Boomsma, D, Heid, IM, Pramstaller, PP, Penninx, BWJH, Janssens, C, Wilson, JF, Spector, T, Martin, NG, Pedersen, NL, Kyvik, KO, Kaprio, J, Hofman, B, Freimer, NB, Jarvelin, MR, Gyllensten, U, Campbell, H, Rudan, I, Johansson, A, Marroni, F, Hayward, C, Vitart, V, Jonasson, I, Pattaro, C, Wright, A, Hastie, N, Pichler, I, Hicks, AA, Falchi, M, Willemsen, G, Hottenga, JJ, de Geus, EJC, Montgomery, GW, Whitfield, J, Magnusson, P, Saharinen, J, Perola, M, Silander, K, Isaacs, A, Sijbrands, EJG , Uitterlinden, A, Witteman, JCM, Oostra, B, Elliott, P, Ruokonen, A, Sabatti, C, Gieger, C, Meitinger, T, Kronenberg, F, Doring, A, Wichmann, HE, Smit, JH, McCarthy, MI, Duijn, C & Peltonen, L 2009, 'Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts', Nature Genetics, vol. 41, no. 1, pp. 47-55. https://doi.org/10.1038/ng.269

TY - JOUR

T1 - Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts

AU - Aulchenko, YS

AU - Ripatti, S

AU - Lindqvist, I

AU - Boomsma, D

AU - Heid, IM

AU - Pramstaller, PP

AU - Penninx, BWJH

AU - Janssens, Cecile

AU - Wilson, JF

AU - Spector, T

AU - Martin, NG

AU - Pedersen, NL

AU - Kyvik, KO

AU - Kaprio, J

AU - Hofman, Bert

AU - Freimer, NB

AU - Jarvelin, MR

AU - Gyllensten, U

AU - Campbell, H

AU - Rudan, I

AU - Johansson, A

AU - Marroni, F

AU - Hayward, C

AU - Vitart, V

AU - Jonasson, I

AU - Pattaro, C

AU - Wright, A

AU - Hastie, N

AU - Pichler, I

AU - Hicks, AA

AU - Falchi, M

AU - Willemsen, G

AU - Hottenga, JJ (Jouke Jan)

AU - de Geus, EJC

AU - Montgomery, GW

AU - Whitfield, J

AU - Magnusson, P

AU - Saharinen, J

AU - Perola, M

AU - Silander, K

AU - Isaacs, Aaron

AU - Sijbrands, E.J.G.

AU - Uitterlinden, André

AU - Witteman, JCM

AU - Oostra, Ben

AU - Elliott, P

AU - Ruokonen, A

AU - Sabatti, C

AU - Gieger, C

AU - Meitinger, T

AU - Kronenberg, F

AU - Doring, A

AU - Wichmann, HE

AU - Smit, JH

AU - McCarthy, MI

AU - Duijn, Cornelia

AU - Peltonen, L

PY - 2009

Y1 - 2009

N2 - Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.

AB - Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.

U2 - 10.1038/ng.269

DO - 10.1038/ng.269

M3 - Article

SN - 1061-4036

VL - 41

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JO - Nature Genetics

JF - Nature Genetics

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