An atlas of genetic influences on human blood metabolites

So-Youn Shin; Eric B Fauman; Ann-Kristin Petersen; Jan Krumsiek; Rita Santos; Jie Huang; Matthias Arnold; Idil Erte; Vincenzo Forgetta; Tsun-Po Yang; Klaudia Walter; Cristina Menni; Lu Chen; Louella Vasquez; Ana M Valdes; Craig L Hyde; Vicky Wang; Daniel Ziemek; Phoebe Roberts; Li Xi; Elin Grundberg; Melanie Waldenberger; J Brent Richards; Robert P Mohney; Michael V Milburn; Sally L John; Jeff Trimmer; Fabian J Theis; John P Overington; Karsten Suhre; M Julia Brosnan; Christian Gieger; Gabi Kastenmüller; Tim D Spector; Nicole Soranzo; Multiple Tissue Human Expression Resource (MuTHER) Consortium

doi:10.1038/ng.2982

An atlas of genetic influences on human blood metabolites

So-Youn Shin, Eric B Fauman, Ann-Kristin Petersen, Jan Krumsiek, Rita Santos, Jie Huang, Matthias Arnold, Idil Erte, Vincenzo Forgetta, Tsun-Po Yang, Klaudia Walter, Cristina Menni, Lu Chen, Louella Vasquez, Ana M Valdes, Craig L Hyde, Vicky Wang, Daniel Ziemek, Phoebe Roberts, Li XiElin Grundberg, Melanie Waldenberger, J Brent Richards, Robert P Mohney, Michael V Milburn, Sally L John, Jeff Trimmer, Fabian J Theis, John P Overington, Karsten Suhre, M Julia Brosnan, Christian Gieger, Gabi Kastenmüller, Tim D Spector, Nicole Soranzo^*, Multiple Tissue Human Expression Resource (MuTHER) Consortium

^*Corresponding author for this work

Twin Research & Genetic Epidemiology

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Abstract

Genome-wide association scans with high-throughput metabolic profiling provide unprecedented insights into how genetic variation influences metabolism and complex disease. Here we report the most comprehensive exploration of genetic loci influencing human metabolism thus far, comprising 7,824 adult individuals from 2 European population studies. We report genome-wide significant associations at 145 metabolic loci and their biochemical connectivity with more than 400 metabolites in human blood. We extensively characterize the resulting in vivo blueprint of metabolism in human blood by integrating it with information on gene expression, heritability and overlap with known loci for complex disorders, inborn errors of metabolism and pharmacological targets. We further developed a database and web-based resources for data mining and results visualization. Our findings provide new insights into the role of inherited variation in blood metabolic diversity and identify potential new opportunities for drug development and for understanding disease.

Original language	English
Pages (from-to)	543-550
Number of pages	8
Journal	Nature Genetics
Volume	46
Issue number	6
Early online date	11 May 2014
DOIs	https://doi.org/10.1038/ng.2982
Publication status	Published - Jun 2014

Keywords

Adolescent
Adult
Aged
Aged, 80 and over
Blood
Blood Chemical Analysis
Cohort Studies
Computational Biology
Data Mining
Europe
Female
Gene Expression Profiling
Genetic Loci
Genetic Variation
Genome-Wide Association Study
Genotype
Germany
Great Britain
Humans
Internet
Male
Metabolism, Inborn Errors
Metabolomics
Middle Aged
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.2982

An atlas of genetic influences_SHIN_Accepted14April2014_GREEN AAMAccepted author manuscript, 2.41 MB

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Shin, S.-Y., Fauman, E. B., Petersen, A.-K., Krumsiek, J., Santos, R., Huang, J., Arnold, M., Erte, I., Forgetta, V., Yang, T.-P., Walter, K., Menni, C., Chen, L., Vasquez, L., Valdes, A. M., Hyde, C. L., Wang, V., Ziemek, D., Roberts, P., ... Multiple Tissue Human Expression Resource (MuTHER) Consortium (2014). An atlas of genetic influences on human blood metabolites. Nature Genetics, 46(6), 543-550. https://doi.org/10.1038/ng.2982

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title = "An atlas of genetic influences on human blood metabolites",

abstract = "Genome-wide association scans with high-throughput metabolic profiling provide unprecedented insights into how genetic variation influences metabolism and complex disease. Here we report the most comprehensive exploration of genetic loci influencing human metabolism thus far, comprising 7,824 adult individuals from 2 European population studies. We report genome-wide significant associations at 145 metabolic loci and their biochemical connectivity with more than 400 metabolites in human blood. We extensively characterize the resulting in vivo blueprint of metabolism in human blood by integrating it with information on gene expression, heritability and overlap with known loci for complex disorders, inborn errors of metabolism and pharmacological targets. We further developed a database and web-based resources for data mining and results visualization. Our findings provide new insights into the role of inherited variation in blood metabolic diversity and identify potential new opportunities for drug development and for understanding disease.",

keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Blood, Blood Chemical Analysis, Cohort Studies, Computational Biology, Data Mining, Europe, Female, Gene Expression Profiling, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Genotype, Germany, Great Britain, Humans, Internet, Male, Metabolism, Inborn Errors, Metabolomics, Middle Aged, Young Adult",

author = "So-Youn Shin and Fauman, {Eric B} and Ann-Kristin Petersen and Jan Krumsiek and Rita Santos and Jie Huang and Matthias Arnold and Idil Erte and Vincenzo Forgetta and Tsun-Po Yang and Klaudia Walter and Cristina Menni and Lu Chen and Louella Vasquez and Valdes, {Ana M} and Hyde, {Craig L} and Vicky Wang and Daniel Ziemek and Phoebe Roberts and Li Xi and Elin Grundberg and Melanie Waldenberger and Richards, {J Brent} and Mohney, {Robert P} and Milburn, {Michael V} and John, {Sally L} and Jeff Trimmer and Theis, {Fabian J} and Overington, {John P} and Karsten Suhre and Brosnan, {M Julia} and Christian Gieger and Gabi Kastenm{\"u}ller and Spector, {Tim D} and Nicole Soranzo and {Multiple Tissue Human Expression Resource (MuTHER) Consortium}",

year = "2014",

month = jun,

doi = "10.1038/ng.2982",

language = "English",

volume = "46",

pages = "543--550",

journal = "Nature Genetics",

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Shin, S-Y, Fauman, EB, Petersen, A-K, Krumsiek, J, Santos, R, Huang, J, Arnold, M, Erte, I, Forgetta, V, Yang, T-P, Walter, K, Menni, C, Chen, L, Vasquez, L, Valdes, AM, Hyde, CL, Wang, V, Ziemek, D, Roberts, P, Xi, L, Grundberg, E, Waldenberger, M, Richards, JB, Mohney, RP, Milburn, MV, John, SL, Trimmer, J, Theis, FJ, Overington, JP, Suhre, K, Brosnan, MJ, Gieger, C, Kastenmüller, G, Spector, TD, Soranzo, N & Multiple Tissue Human Expression Resource (MuTHER) Consortium 2014, 'An atlas of genetic influences on human blood metabolites', Nature Genetics, vol. 46, no. 6, pp. 543-550. https://doi.org/10.1038/ng.2982

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AU - Santos, Rita

AU - Huang, Jie

AU - Arnold, Matthias

AU - Erte, Idil

AU - Forgetta, Vincenzo

AU - Yang, Tsun-Po

AU - Walter, Klaudia

AU - Menni, Cristina

AU - Chen, Lu

AU - Vasquez, Louella

AU - Valdes, Ana M

AU - Hyde, Craig L

AU - Wang, Vicky

AU - Ziemek, Daniel

AU - Roberts, Phoebe

AU - Xi, Li

AU - Grundberg, Elin

AU - Waldenberger, Melanie

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AU - Mohney, Robert P

AU - Milburn, Michael V

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AU - Trimmer, Jeff

AU - Theis, Fabian J

AU - Overington, John P

AU - Suhre, Karsten

AU - Brosnan, M Julia

AU - Gieger, Christian

AU - Kastenmüller, Gabi

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AU - Soranzo, Nicole

AU - Multiple Tissue Human Expression Resource (MuTHER) Consortium

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N2 - Genome-wide association scans with high-throughput metabolic profiling provide unprecedented insights into how genetic variation influences metabolism and complex disease. Here we report the most comprehensive exploration of genetic loci influencing human metabolism thus far, comprising 7,824 adult individuals from 2 European population studies. We report genome-wide significant associations at 145 metabolic loci and their biochemical connectivity with more than 400 metabolites in human blood. We extensively characterize the resulting in vivo blueprint of metabolism in human blood by integrating it with information on gene expression, heritability and overlap with known loci for complex disorders, inborn errors of metabolism and pharmacological targets. We further developed a database and web-based resources for data mining and results visualization. Our findings provide new insights into the role of inherited variation in blood metabolic diversity and identify potential new opportunities for drug development and for understanding disease.

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KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Blood

KW - Blood Chemical Analysis

KW - Cohort Studies

KW - Computational Biology

KW - Data Mining

KW - Europe

KW - Female

KW - Gene Expression Profiling

KW - Genetic Loci

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - Genotype

KW - Germany

KW - Great Britain

KW - Humans

KW - Internet

KW - Male

KW - Metabolism, Inborn Errors

KW - Metabolomics

KW - Middle Aged

KW - Young Adult

U2 - 10.1038/ng.2982

DO - 10.1038/ng.2982

M3 - Article

C2 - 24816252

SN - 1061-4036

VL - 46

SP - 543

EP - 550

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

An atlas of genetic influences on human blood metabolites

Abstract

Keywords

UN SDGs

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