Literature DB >> 27777320

Associations of genetic variants for adult lipid levels with lipid levels in children. The Generation R Study.

Ardashel Latsuzbaia1, Vincent W V Jaddoe1,2,3, Albert Hofman2, Oscar H Franco2, Janine F Felix4,2,3.   

Abstract

Lipid concentrations are heritable traits. Recently, the number of known genetic loci associated with lipid levels in adults increased from 95 to 157. The effects of these 157 loci have not been tested in children. Considering that lipid levels track from childhood to adulthood, we studied to determine whether these variants already affected lipid concentrations in a large group of 2,645 children with a median age of 6.0 years (95% range 5.7-7.3 years) from the population-based Generation R Study. Twenty-eight SNPs associated with TGs, 39 SNPs associated with total cholesterol (TC), 28 SNPs associated with LDL cholesterol (LDL-C), and 56 SNPs associated with HDL cholesterol (HDL-C) were analyzed individually and combined into genetic risk scores (GRSs). All risk scores were associated with their specific outcomes. The differences in mean absolute lipid and lipoprotein values between the 10% of children with the highest lipid or lipoprotein GRS versus the 10% with the lowest score were 0.28, 0.25, 0.32, and 0.30 mmol/l for TGs, TC, LDL-C, and HDL-C, respectively. In conclusion, we show for the first time that GRSs based on 157 SNPs associated with adult lipid concentrations are associated with lipid levels in children. The genetic background of these phenotypes at least partly overlaps between children and adults.
Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Entities:  

Keywords:  cholesterol; dyslipidemias; genetic risk score; genetics; high density lipoprotein; low density lipoprotein; triglycerides

Mesh:

Substances:

Year:  2016        PMID: 27777320      PMCID: PMC5321224          DOI: 10.1194/jlr.P066902

Source DB:  PubMed          Journal:  J Lipid Res        ISSN: 0022-2275            Impact factor:   5.922


  40 in total

1.  A haplotype map of the human genome.

Authors: 
Journal:  Nature       Date:  2005-10-27       Impact factor: 49.962

2.  The Generation R Study: Biobank update 2015.

Authors:  Claudia J Kruithof; Marjolein N Kooijman; Cornelia M van Duijn; Oscar H Franco; Johan C de Jongste; Caroline C W Klaver; Johan P Mackenbach; Henriëtte A Moll; Hein Raat; Edmond H H M Rings; Fernando Rivadeneira; Eric A P Steegers; Henning Tiemeier; Andre G Uitterlinden; Frank C Verhulst; Eppo B Wolvius; Albert Hofman; Vincent W V Jaddoe
Journal:  Eur J Epidemiol       Date:  2014-12-21       Impact factor: 8.082

3.  Relation of lipid gene scores to longitudinal trends in lipid levels and incidence of abnormal lipid levels among individuals of European ancestry: the Atherosclerosis Risk in Communities (ARIC) study.

Authors:  Pamela L Lutsey; Laura J Rasmussen-Torvik; James S Pankow; Alvaro Alonso; Derek J Smolenski; Weihong Tang; Josef Coresh; Kelly A Volcik; Christie M Ballantyne; Eric Boerwinkle; Aaron R Folsom
Journal:  Circ Cardiovasc Genet       Date:  2011-11-04

4.  Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice. Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes.

Authors:  P H Weinstock; C L Bisgaier; K Aalto-Setälä; H Radner; R Ramakrishnan; S Levak-Frank; A D Essenburg; R Zechner; J L Breslow
Journal:  J Clin Invest       Date:  1995-12       Impact factor: 14.808

5.  A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits.

Authors:  H Okamoto; F Yonemori; K Wakitani; T Minowa; K Maeda; H Shinkai
Journal:  Nature       Date:  2000-07-13       Impact factor: 49.962

Review 6.  Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk.

Authors:  Alexander Thompson; Emanuele Di Angelantonio; Nadeem Sarwar; Sebhat Erqou; Danish Saleheen; Robin P F Dullaart; Bernard Keavney; Zheng Ye; John Danesh
Journal:  JAMA       Date:  2008-06-18       Impact factor: 56.272

7.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.

Authors:  C Baigent; L Blackwell; J Emberson; L E Holland; C Reith; N Bhala; R Peto; E H Barnes; A Keech; J Simes; R Collins
Journal:  Lancet       Date:  2010-11-08       Impact factor: 79.321

8.  A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study.

Authors:  Sekar Kathiresan; Alisa K Manning; Serkalem Demissie; Ralph B D'Agostino; Aarti Surti; Candace Guiducci; Lauren Gianniny; Nöel P Burtt; Olle Melander; Marju Orho-Melander; Donna K Arnett; Gina M Peloso; Jose M Ordovas; L Adrienne Cupples
Journal:  BMC Med Genet       Date:  2007-09-19       Impact factor: 2.103

9.  Challenges in conducting genome-wide association studies in highly admixed multi-ethnic populations: the Generation R Study.

Authors:  Carolina Medina-Gomez; Janine Frédérique Felix; Karol Estrada; Marjoline Josephine Peters; Lizbeth Herrera; Claudia Jeanette Kruithof; Liesbeth Duijts; Albert Hofman; Cornelia Marja van Duijn; Andreas Gerardus Uitterlinden; Vincent Wilfred Vishal Jaddoe; Fernando Rivadeneira
Journal:  Eur J Epidemiol       Date:  2015-03-12       Impact factor: 8.082

10.  Discovery and refinement of loci associated with lipid levels.

Authors:  Cristen J Willer; Ellen M Schmidt; Sebanti Sengupta; Michael Boehnke; Panos Deloukas; Sekar Kathiresan; Karen L Mohlke; Erik Ingelsson; Gonçalo R Abecasis; 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; Åsa 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; Martina Müller-Nurasyid; Ilja M Nolte; Jeffrey R O'Connell; Cameron D Palmer; Markus Perola; Ann-Kristin Petersen; Serena Sanna; Richa Saxena; Susan K Service; Sonia Shah; Dmitry Shungin; Carlo Sidore; Ci Song; Rona J Strawbridge; Ida Surakka; Toshiko Tanaka; Tanya M Teslovich; Gudmar Thorleifsson; Evita G Van den Herik; Benjamin F Voight; Kelly A Volcik; Lindsay L Waite; Andrew Wong; Ying Wu; Weihua Zhang; Devin Absher; Gershim Asiki; Inês Barroso; Latonya F Been; Jennifer L Bolton; Lori L Bonnycastle; Paolo Brambilla; Mary S Burnett; Giancarlo Cesana; Maria Dimitriou; Alex S F Doney; Angela Döring; Paul Elliott; Stephen E Epstein; Gudmundur Ingi Eyjolfsson; Bruna Gigante; Mark O Goodarzi; Harald Grallert; Martha L Gravito; Christopher J Groves; Göran Hallmans; Anna-Liisa Hartikainen; Caroline Hayward; Dena Hernandez; Andrew A Hicks; Hilma Holm; Yi-Jen Hung; Thomas Illig; Michelle R Jones; Pontiano Kaleebu; John J P Kastelein; Kay-Tee Khaw; Eric Kim; Norman Klopp; Pirjo Komulainen; Meena Kumari; Claudia Langenberg; Terho Lehtimäki; Shih-Yi Lin; Jaana Lindström; Ruth J F Loos; François Mach; Wendy L McArdle; Christa Meisinger; Braxton D Mitchell; Gabrielle Müller; Ramaiah Nagaraja; Narisu Narisu; Tuomo V M Nieminen; Rebecca N Nsubuga; Isleifur Olafsson; Ken K Ong; Aarno Palotie; Theodore Papamarkou; Cristina Pomilla; Anneli Pouta; Daniel J Rader; Muredach P Reilly; Paul M Ridker; Fernando Rivadeneira; Igor Rudan; Aimo Ruokonen; Nilesh Samani; Hubert Scharnagl; Janet Seeley; Kaisa Silander; Alena Stančáková; Kathleen Stirrups; Amy J Swift; Laurence Tiret; Andre G Uitterlinden; L Joost van Pelt; Sailaja Vedantam; Nicholas Wainwright; Cisca Wijmenga; Sarah H Wild; Gonneke Willemsen; Tom Wilsgaard; James F Wilson; Elizabeth H Young; Jing Hua Zhao; Linda S Adair; Dominique Arveiler; Themistocles L Assimes; Stefania Bandinelli; Franklyn Bennett; Murielle Bochud; Bernhard O Boehm; Dorret I Boomsma; Ingrid B Borecki; Stefan R Bornstein; Pascal Bovet; Michel Burnier; Harry Campbell; Aravinda Chakravarti; John C Chambers; Yii-Der Ida Chen; Francis S Collins; Richard S Cooper; John Danesh; George Dedoussis; Ulf de Faire; Alan B Feranil; Jean Ferrières; Luigi Ferrucci; Nelson B Freimer; Christian Gieger; Leif C Groop; Vilmundur Gudnason; Ulf Gyllensten; Anders Hamsten; Tamara B Harris; Aroon Hingorani; Joel N Hirschhorn; Albert Hofman; G Kees Hovingh; Chao Agnes Hsiung; Steve E Humphries; Steven C Hunt; Kristian Hveem; Carlos Iribarren; Marjo-Riitta Järvelin; Antti Jula; Mika Kähönen; Jaakko Kaprio; Antero Kesäniemi; Mika Kivimaki; Jaspal S Kooner; Peter J Koudstaal; Ronald M Krauss; Diana Kuh; Johanna Kuusisto; Kirsten O Kyvik; Markku Laakso; Timo A Lakka; Lars Lind; Cecilia M Lindgren; Nicholas G Martin; Winfried März; Mark I McCarthy; Colin A McKenzie; Pierre Meneton; Andres Metspalu; Leena Moilanen; Andrew D Morris; Patricia B Munroe; Inger Njølstad; Nancy L Pedersen; Chris Power; Peter P Pramstaller; Jackie F Price; Bruce M Psaty; Thomas Quertermous; Rainer Rauramaa; Danish Saleheen; Veikko Salomaa; Dharambir K Sanghera; Jouko Saramies; Peter E H Schwarz; Wayne H-H Sheu; Alan R Shuldiner; Agneta Siegbahn; Tim D Spector; Kari Stefansson; David P Strachan; Bamidele O Tayo; Elena Tremoli; Jaakko Tuomilehto; Matti Uusitupa; Cornelia M van Duijn; Peter Vollenweider; Lars Wallentin; Nicholas J Wareham; John B Whitfield; Bruce H R Wolffenbuttel; Jose M Ordovas; Eric Boerwinkle; Colin N A Palmer; Unnur Thorsteinsdottir; Daniel I Chasman; Jerome I Rotter; Paul W Franks; Samuli Ripatti; L Adrienne Cupples; Manjinder S Sandhu; Stephen S Rich
Journal:  Nat Genet       Date:  2013-10-06       Impact factor: 38.330

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1.  Polygenic Risk of Hypertriglyceridemia Is Modified by BMI.

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Journal:  Int J Mol Sci       Date:  2022-08-30       Impact factor: 6.208

Review 2.  Genetics of Hypertriglyceridemia.

Authors:  Jacqueline S Dron; Robert A Hegele
Journal:  Front Endocrinol (Lausanne)       Date:  2020-07-24       Impact factor: 5.555

3.  Direct and indirect genetic effects on triglycerides through omics and correlated phenotypes.

Authors:  Anne E Justice; Annie Green Howard; Lindsay Fernández-Rhodes; Misa Graff; Ran Tao; Kari E North
Journal:  BMC Proc       Date:  2018-09-17
  3 in total

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