Skip to main content
Erschienen in: European Journal of Nutrition 4/2017

01.03.2016 | Original Contribution

Meta-analysis of genome-wide association studies identifies three novel loci for saturated fatty acids in East Asians

verfasst von: Jingwen Zhu, Ani Manichaikul, Yao Hu, Yii-Der I. Chen, Shuang Liang, Lyn M. Steffen, Stephen S. Rich, Michael Tsai, David S. Siscovick, Rozenn N. Lemaitre, Huaixing Li, Xu Lin

Erschienen in: European Journal of Nutrition | Ausgabe 4/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

We aimed to characterize common genetic variants that influence saturated fatty acid concentrations in East Asians.

Methods

Meta-analysis of genome-wide association studies for circulating SFAs was conducted in two population-based cohorts comprising 3521 participants of Chinese ancestry.

Results

We identified two novel 14:0-associated loci at LMX1A (LIM homeobox transcription factor 1) and AMPD3 (AMP deaminase 3) (P = 5.08 × 10−9 and P = 4.33 × 10−8, respectively), and a novel 20:0-associated locus at CERS4 (ceramide synthase 4) (P = 1.76 × 10−10). We also confirmed the previously reported association of FADS1/2-rs102275 with 18:0 (P = 1.12 × 10−5). In addition, the A alleles of rs11042834 in AMPD3 and rs17159388 in CERS4 also exhibited evidence of associations with high-density lipoprotein cholesterol (P = 0.0162 and P = 0.0161, respectively).

Conclusions

To our knowledge, this is the first GWAS analysis to examine SFA concentrations in East Asian populations. Our findings provide novel evidence that genetic variations of several genes from multiple pathways are associated with SFA concentrations in human body.
Literatur
2.
Zurück zum Zitat Wang L, Folsom AR, Eckfeldt JH (2003) Plasma fatty acid composition and incidence of coronary heart disease in middle aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Nutr Metab Cardiovasc Dis NMCD 13:256–266. doi:10.1016/S0939-4753(03)80029-7 CrossRef Wang L, Folsom AR, Eckfeldt JH (2003) Plasma fatty acid composition and incidence of coronary heart disease in middle aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Nutr Metab Cardiovasc Dis NMCD 13:256–266. doi:10.​1016/​S0939-4753(03)80029-7 CrossRef
3.
Zurück zum Zitat Khaw KT, Friesen MD, Riboli E, Luben R, Wareham N (2012) Plasma phospholipid fatty acid concentration and incident coronary heart disease in men and women: the EPIC-Norfolk prospective study. PLoS Med 9:e1001255. doi:10.1371/journal.pmed.1001255 CrossRef Khaw KT, Friesen MD, Riboli E, Luben R, Wareham N (2012) Plasma phospholipid fatty acid concentration and incident coronary heart disease in men and women: the EPIC-Norfolk prospective study. PLoS Med 9:e1001255. doi:10.​1371/​journal.​pmed.​1001255 CrossRef
4.
Zurück zum Zitat Kroger J, Zietemann V, Enzenbach C, Weikert C, Jansen EH, Doring F, Joost HG, Boeing H, Schulze MB (2011) Erythrocyte membrane phospholipid fatty acids, desaturase activity, and dietary fatty acids in relation to risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Am J Clin Nutr 93:127–142. doi:10.3945/ajcn.110.005447 CrossRef Kroger J, Zietemann V, Enzenbach C, Weikert C, Jansen EH, Doring F, Joost HG, Boeing H, Schulze MB (2011) Erythrocyte membrane phospholipid fatty acids, desaturase activity, and dietary fatty acids in relation to risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Am J Clin Nutr 93:127–142. doi:10.​3945/​ajcn.​110.​005447 CrossRef
5.
Zurück zum Zitat Yamagishi K, Nettleton JA, Folsom AR, Investigators AS (2008) Plasma fatty acid composition and incident heart failure in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J156:965–974. doi:10.1016/j.ahj.2008.06.017 CrossRef Yamagishi K, Nettleton JA, Folsom AR, Investigators AS (2008) Plasma fatty acid composition and incident heart failure in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J156:965–974. doi:10.​1016/​j.​ahj.​2008.​06.​017 CrossRef
6.
Zurück zum Zitat Yaemsiri S, Sen S, Tinker LF, Robinson WR, Evans RW, Rosamond W, Wasserthiel-Smoller S, He K (2013) Serum fatty acids and incidence of ischemic stroke among postmenopausal women. Stroke 44:2710–2717. doi:10.1161/STROKEAHA.111.000834 CrossRef Yaemsiri S, Sen S, Tinker LF, Robinson WR, Evans RW, Rosamond W, Wasserthiel-Smoller S, He K (2013) Serum fatty acids and incidence of ischemic stroke among postmenopausal women. Stroke 44:2710–2717. doi:10.​1161/​STROKEAHA.​111.​000834 CrossRef
8.
Zurück zum Zitat de Oliveira Otto MC, Nettleton JA, Lemaitre RN, Steffen LM, Kromhout D, Rich SS, Tsai MY, Jacobs DR, Mozaffarian D (2013) Biomarkers of dairy fatty acids and risk of cardiovascular disease in the multi-ethnic study of atherosclerosis. J Am Heart Assoc 2:e000092. doi:10.1161/JAHA.113.000092 de Oliveira Otto MC, Nettleton JA, Lemaitre RN, Steffen LM, Kromhout D, Rich SS, Tsai MY, Jacobs DR, Mozaffarian D (2013) Biomarkers of dairy fatty acids and risk of cardiovascular disease in the multi-ethnic study of atherosclerosis. J Am Heart Assoc 2:e000092. doi:10.​1161/​JAHA.​113.​000092
9.
Zurück zum Zitat Wu JH, Lemaitre RN, Manichaikul A, Guan W, Tanaka T, Foy M, Kabagambe EK, Djousse L, Siscovick D, Fretts AM et al (2013) Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium. Circ Cardiovasc Genet 6:171–183. doi:10.1161/CIRCGENETICS.112.964619 CrossRef Wu JH, Lemaitre RN, Manichaikul A, Guan W, Tanaka T, Foy M, Kabagambe EK, Djousse L, Siscovick D, Fretts AM et al (2013) Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium. Circ Cardiovasc Genet 6:171–183. doi:10.​1161/​CIRCGENETICS.​112.​964619 CrossRef
10.
Zurück zum Zitat Ameur A, Enroth S, Johansson A, Zaboli G, Igl W, Johansson AC, Rivas MA, Daly MJ, Schmitz G, Hicks AA et al (2012) Genetic adaptation of fatty-acid metabolism: a human-specific haplotype increasing the biosynthesis of long-chain omega-3 and omega-6 fatty acids. Am J Hum Genet 90:809–820. doi:10.1016/j.ajhg.2012.03.014 CrossRef Ameur A, Enroth S, Johansson A, Zaboli G, Igl W, Johansson AC, Rivas MA, Daly MJ, Schmitz G, Hicks AA et al (2012) Genetic adaptation of fatty-acid metabolism: a human-specific haplotype increasing the biosynthesis of long-chain omega-3 and omega-6 fatty acids. Am J Hum Genet 90:809–820. doi:10.​1016/​j.​ajhg.​2012.​03.​014 CrossRef
11.
Zurück zum Zitat Ye X, Yu Z, Li H, Franco OH, Liu Y, Lin X (2007) Distributions of C-reactive protein and its association with metabolic syndrome in middle-aged and older Chinese people. J Am Coll Cardiol 49:1798–1805. doi:10.1016/j.jacc.2007.01.065 CrossRef Ye X, Yu Z, Li H, Franco OH, Liu Y, Lin X (2007) Distributions of C-reactive protein and its association with metabolic syndrome in middle-aged and older Chinese people. J Am Coll Cardiol 49:1798–1805. doi:10.​1016/​j.​jacc.​2007.​01.​065 CrossRef
12.
Zurück zum Zitat Bild DE, Bluemke DA, Burke GL, Detrano R, Diez Roux AV, Folsom AR, Greenland P, Jacob DR Jr, Kronmal R, Liu K et al (2002) Multi-ethnic study of atherosclerosis: objectives and design. Am J Epidemiol 156:871–881. doi:10.1093/aje/kwf113 CrossRef Bild DE, Bluemke DA, Burke GL, Detrano R, Diez Roux AV, Folsom AR, Greenland P, Jacob DR Jr, Kronmal R, Liu K et al (2002) Multi-ethnic study of atherosclerosis: objectives and design. Am J Epidemiol 156:871–881. doi:10.​1093/​aje/​kwf113 CrossRef
13.
Zurück zum Zitat Zong G, Ye X, Sun L, Li H, Yu Z, Hu FB, Sun Q, Lin X (2012) Associations of erythrocyte palmitoleic acid with adipokines, inflammatory markers, and the metabolic syndrome in middle-aged and older Chinese. Am J Clin Nutr 96:970–976. doi:10.3945/ajcn.112.040204 CrossRef Zong G, Ye X, Sun L, Li H, Yu Z, Hu FB, Sun Q, Lin X (2012) Associations of erythrocyte palmitoleic acid with adipokines, inflammatory markers, and the metabolic syndrome in middle-aged and older Chinese. Am J Clin Nutr 96:970–976. doi:10.​3945/​ajcn.​112.​040204 CrossRef
15.
Zurück zum Zitat Marchini J, Howie B, Myers S, McVean G, Donnelly P (2007) A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet 39:906–913. doi:10.1038/ng2088 CrossRef Marchini J, Howie B, Myers S, McVean G, Donnelly P (2007) A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet 39:906–913. doi:10.​1038/​ng2088 CrossRef
17.
Zurück zum Zitat Devlin B, Roeder K (1999) Genomic control for association studies. Biometrics 55:997–1004CrossRef Devlin B, Roeder K (1999) Genomic control for association studies. Biometrics 55:997–1004CrossRef
18.
Zurück zum Zitat German MS, Wang J, Fernald AA, Espinosa R 3rd, Le Beau MM, Bell GI (1994) Localization of the genes encoding two transcription factors, LMX1 and CDX3, regulating insulin gene expression to human chromosomes 1 and 13. Genomics 24:403–404. doi:10.1006/geno.1994.1639 CrossRef German MS, Wang J, Fernald AA, Espinosa R 3rd, Le Beau MM, Bell GI (1994) Localization of the genes encoding two transcription factors, LMX1 and CDX3, regulating insulin gene expression to human chromosomes 1 and 13. Genomics 24:403–404. doi:10.​1006/​geno.​1994.​1639 CrossRef
19.
20.
Zurück zum Zitat Johnson JD, Zhang W, Rudnick A, Rutter WJ, German MS (1997) Transcriptional synergy between LIM-homeodomain proteins and basic helix-loop-helix proteins: the LIM2 domain determines specificity. Mol Cell Biol 17:3488–3496CrossRef Johnson JD, Zhang W, Rudnick A, Rutter WJ, German MS (1997) Transcriptional synergy between LIM-homeodomain proteins and basic helix-loop-helix proteins: the LIM2 domain determines specificity. Mol Cell Biol 17:3488–3496CrossRef
21.
Zurück zum Zitat Roberts R, Hodson L, Dennis AL, Neville MJ, Humphreys SM, Harnden KE, Micklem KJ, Frayn KN (2009) Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans. Diabetologia 52:882–890. doi:10.1007/s00125-009-1300-4 CrossRef Roberts R, Hodson L, Dennis AL, Neville MJ, Humphreys SM, Harnden KE, Micklem KJ, Frayn KN (2009) Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans. Diabetologia 52:882–890. doi:10.​1007/​s00125-009-1300-4 CrossRef
22.
Zurück zum Zitat Ebbesson SO, Tejero ME, Lopez-Alvarenga JC, Harris WS, Ebbesson LO, Devereux RB, MacCluer JW, Wenger C, Laston S, Fabsitz RR et al (2010) Individual saturated fatty acids are associated with different components of insulin resistance and glucose metabolism: the GOCADAN study. Int J Circumpolar Health 69:344–351CrossRef Ebbesson SO, Tejero ME, Lopez-Alvarenga JC, Harris WS, Ebbesson LO, Devereux RB, MacCluer JW, Wenger C, Laston S, Fabsitz RR et al (2010) Individual saturated fatty acids are associated with different components of insulin resistance and glucose metabolism: the GOCADAN study. Int J Circumpolar Health 69:344–351CrossRef
23.
Zurück zum Zitat Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ et al (2010) Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466:707–713. doi:10.1038/nature09270 CrossRef Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ et al (2010) Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466:707–713. doi:10.​1038/​nature09270 CrossRef
25.
Zurück zum Zitat Lanaspa MA, Sanchez-Lozada LG, Choi YJ, Cicerchi C, Kanbay M, Roncal-Jimenez CA, Ishimoto T, Li N, Marek G, Duranay M et al (2012) Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver. J Biol Chem 287:40732–40744. doi:10.1074/jbc.M112.399899 CrossRef Lanaspa MA, Sanchez-Lozada LG, Choi YJ, Cicerchi C, Kanbay M, Roncal-Jimenez CA, Ishimoto T, Li N, Marek G, Duranay M et al (2012) Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver. J Biol Chem 287:40732–40744. doi:10.​1074/​jbc.​M112.​399899 CrossRef
26.
Zurück zum Zitat Hicks AA, Pramstaller PP, Johansson A, Vitart V, Rudan I, Ugocsai P, Aulchenko Y, Franklin CS, Liebisch G, Erdmann J et al (2009) Genetic determinants of circulating sphingolipid concentrations in European populations. PLoS Genet 5:e1000672. doi:10.1371/journal.pgen.1000672 CrossRef Hicks AA, Pramstaller PP, Johansson A, Vitart V, Rudan I, Ugocsai P, Aulchenko Y, Franklin CS, Liebisch G, Erdmann J et al (2009) Genetic determinants of circulating sphingolipid concentrations in European populations. PLoS Genet 5:e1000672. doi:10.​1371/​journal.​pgen.​1000672 CrossRef
27.
Zurück zum Zitat Demirkan A, van Duijn CM, Ugocsai P, Isaacs A, Pramstaller PP, Liebisch G, Wilson JF, Johansson A, Rudan I, Aulchenko YS et al (2012) Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations. PLoS Genet 8:e1002490. doi:10.1371/journal.pgen.1002490 CrossRef Demirkan A, van Duijn CM, Ugocsai P, Isaacs A, Pramstaller PP, Liebisch G, Wilson JF, Johansson A, Rudan I, Aulchenko YS et al (2012) Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations. PLoS Genet 8:e1002490. doi:10.​1371/​journal.​pgen.​1002490 CrossRef
28.
Zurück zum Zitat Lemaitre RN, King IB, Kabagambe EK, Wu JH, McKnight B, Manichaikul A, Guan W, Sun Q, Chasman DI, Foy M et al (2015) Genetic loci associated with circulating levels of very long-chain saturated fatty acids. JLipid Res 56:176–184. doi:10.1194/jlr.M052456 CrossRef Lemaitre RN, King IB, Kabagambe EK, Wu JH, McKnight B, Manichaikul A, Guan W, Sun Q, Chasman DI, Foy M et al (2015) Genetic loci associated with circulating levels of very long-chain saturated fatty acids. JLipid Res 56:176–184. doi:10.​1194/​jlr.​M052456 CrossRef
29.
Zurück zum Zitat Mizutani Y, Kihara A, Igarashi Y (2005) Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem J 390:263–271. doi:10.1042/BJ20050291 CrossRef Mizutani Y, Kihara A, Igarashi Y (2005) Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem J 390:263–271. doi:10.​1042/​BJ20050291 CrossRef
Metadaten
Titel
Meta-analysis of genome-wide association studies identifies three novel loci for saturated fatty acids in East Asians
verfasst von
Jingwen Zhu
Ani Manichaikul
Yao Hu
Yii-Der I. Chen
Shuang Liang
Lyn M. Steffen
Stephen S. Rich
Michael Tsai
David S. Siscovick
Rozenn N. Lemaitre
Huaixing Li
Xu Lin
Publikationsdatum
01.03.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nutrition / Ausgabe 4/2017
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-016-1193-1

Weitere Artikel der Ausgabe 4/2017

European Journal of Nutrition 4/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.