Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA
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Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA. / Kettunen, Johannes; Demirkan, Ayşe; Würtz, Peter; Draisma, Harmen H M; Haller, Toomas; Rawal, Rajesh; Vaarhorst, Anika; Kangas, Antti J; Lyytikäinen, Leo-Pekka; Pirinen, Matti; Pool, René; Sarin, Antti-Pekka; Soininen, Pasi; Tukiainen, Taru; Wang, Qin; Tiainen, Mika; Tynkkynen, Tuulia; Amin, Najaf; Zeller, Tanja; Beekman, Marian; Deelen, Joris; van Dijk, Ko Willems; Esko, Tõnu; Hottenga, Jouke-Jan; van Leeuwen, Elisabeth M; Lehtimäki, Terho; Mihailov, Evelin; Rose, Richard J; de Craen, Anton J M; Gieger, Christian; Kähönen, Mika; Perola, Markus; Blankenberg, Stefan; Savolainen, Markku J; Verhoeven, Aswin; Viikari, Jorma; Willemsen, Gonneke; Boomsma, Dorret I; van Duijn, Cornelia M; Eriksson, Johan; Jula, Antti; Järvelin, Marjo-Riitta; Kaprio, Jaakko; Metspalu, Andres; Raitakari, Olli; Salomaa, Veikko; Slagboom, P Eline; Waldenberger, Melanie; Ripatti, Samuli; Ala-Korpela, Mika.
In: NAT COMMUN, Vol. 7, 23.03.2016, p. 11122.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA
AU - Kettunen, Johannes
AU - Demirkan, Ayşe
AU - Würtz, Peter
AU - Draisma, Harmen H M
AU - Haller, Toomas
AU - Rawal, Rajesh
AU - Vaarhorst, Anika
AU - Kangas, Antti J
AU - Lyytikäinen, Leo-Pekka
AU - Pirinen, Matti
AU - Pool, René
AU - Sarin, Antti-Pekka
AU - Soininen, Pasi
AU - Tukiainen, Taru
AU - Wang, Qin
AU - Tiainen, Mika
AU - Tynkkynen, Tuulia
AU - Amin, Najaf
AU - Zeller, Tanja
AU - Beekman, Marian
AU - Deelen, Joris
AU - van Dijk, Ko Willems
AU - Esko, Tõnu
AU - Hottenga, Jouke-Jan
AU - van Leeuwen, Elisabeth M
AU - Lehtimäki, Terho
AU - Mihailov, Evelin
AU - Rose, Richard J
AU - de Craen, Anton J M
AU - Gieger, Christian
AU - Kähönen, Mika
AU - Perola, Markus
AU - Blankenberg, Stefan
AU - Savolainen, Markku J
AU - Verhoeven, Aswin
AU - Viikari, Jorma
AU - Willemsen, Gonneke
AU - Boomsma, Dorret I
AU - van Duijn, Cornelia M
AU - Eriksson, Johan
AU - Jula, Antti
AU - Järvelin, Marjo-Riitta
AU - Kaprio, Jaakko
AU - Metspalu, Andres
AU - Raitakari, Olli
AU - Salomaa, Veikko
AU - Slagboom, P Eline
AU - Waldenberger, Melanie
AU - Ripatti, Samuli
AU - Ala-Korpela, Mika
PY - 2016/3/23
Y1 - 2016/3/23
N2 - Genome-wide association studies have identified numerous loci linked with complex diseases, for which the molecular mechanisms remain largely unclear. Comprehensive molecular profiling of circulating metabolites captures highly heritable traits, which can help to uncover metabolic pathophysiology underlying established disease variants. We conduct an extended genome-wide association study of genetic influences on 123 circulating metabolic traits quantified by nuclear magnetic resonance metabolomics from up to 24,925 individuals and identify eight novel loci for amino acids, pyruvate and fatty acids. The LPA locus link with cardiovascular risk exemplifies how detailed metabolic profiling may inform underlying aetiology via extensive associations with very-low-density lipoprotein and triglyceride metabolism. Genetic fine mapping and Mendelian randomization uncover wide-spread causal effects of lipoprotein(a) on overall lipoprotein metabolism and we assess potential pleiotropic consequences of genetically elevated lipoprotein(a) on diverse morbidities via electronic health-care records. Our findings strengthen the argument for safe LPA-targeted intervention to reduce cardiovascular risk.
AB - Genome-wide association studies have identified numerous loci linked with complex diseases, for which the molecular mechanisms remain largely unclear. Comprehensive molecular profiling of circulating metabolites captures highly heritable traits, which can help to uncover metabolic pathophysiology underlying established disease variants. We conduct an extended genome-wide association study of genetic influences on 123 circulating metabolic traits quantified by nuclear magnetic resonance metabolomics from up to 24,925 individuals and identify eight novel loci for amino acids, pyruvate and fatty acids. The LPA locus link with cardiovascular risk exemplifies how detailed metabolic profiling may inform underlying aetiology via extensive associations with very-low-density lipoprotein and triglyceride metabolism. Genetic fine mapping and Mendelian randomization uncover wide-spread causal effects of lipoprotein(a) on overall lipoprotein metabolism and we assess potential pleiotropic consequences of genetically elevated lipoprotein(a) on diverse morbidities via electronic health-care records. Our findings strengthen the argument for safe LPA-targeted intervention to reduce cardiovascular risk.
KW - Adult
KW - Aged
KW - Cardiovascular Diseases/genetics
KW - Chromosome Mapping
KW - Female
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Humans
KW - Lipoprotein(a)/genetics
KW - Lipoproteins, VLDL/metabolism
KW - Magnetic Resonance Spectroscopy
KW - Male
KW - Mendelian Randomization Analysis
KW - Metabolomics/methods
KW - Middle Aged
KW - Triglycerides/metabolism
KW - Young Adult
U2 - 10.1038/ncomms11122
DO - 10.1038/ncomms11122
M3 - SCORING: Journal article
C2 - 27005778
VL - 7
SP - 11122
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
ER -