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Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans

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Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans. / Lemmelä, Susanna; Wigmore, Eleanor M; Benner, Christian; Havulinna, Aki S; Ong, Rachel M Y; Kempf, Tibor; Wollert, Kai C; Blankenberg, Stefan; Zeller, Tanja; Peters, James E; Salomaa, Veikko; Fritsch, Maria; March, Ruth; Palotie, Aarno; Daly, Mark; Butterworth, Adam S; Kinnunen, Mervi; Paul, Dirk S; Matakidou, Athena.

In: ELIFE, Vol. 11, e76272, 02.08.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lemmelä, S, Wigmore, EM, Benner, C, Havulinna, AS, Ong, RMY, Kempf, T, Wollert, KC, Blankenberg, S, Zeller, T, Peters, JE, Salomaa, V, Fritsch, M, March, R, Palotie, A, Daly, M, Butterworth, AS, Kinnunen, M, Paul, DS & Matakidou, A 2022, 'Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans', ELIFE, vol. 11, e76272. https://doi.org/10.7554/eLife.76272

APA

Lemmelä, S., Wigmore, E. M., Benner, C., Havulinna, A. S., Ong, R. M. Y., Kempf, T., Wollert, K. C., Blankenberg, S., Zeller, T., Peters, J. E., Salomaa, V., Fritsch, M., March, R., Palotie, A., Daly, M., Butterworth, A. S., Kinnunen, M., Paul, D. S., & Matakidou, A. (2022). Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans. ELIFE, 11, [e76272]. https://doi.org/10.7554/eLife.76272

Vancouver

Lemmelä S, Wigmore EM, Benner C, Havulinna AS, Ong RMY, Kempf T et al. Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans. ELIFE. 2022 Aug 2;11. e76272. https://doi.org/10.7554/eLife.76272

Bibtex

@article{30908ecf9366411f97a3a3f1a0894bd0,
title = "Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans",
abstract = "Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in GDF15, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW pFDR = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.",
keywords = "Biomarkers, Body Mass Index, Cardiovascular Diseases/genetics, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis",
author = "Susanna Lemmel{\"a} and Wigmore, {Eleanor M} and Christian Benner and Havulinna, {Aki S} and Ong, {Rachel M Y} and Tibor Kempf and Wollert, {Kai C} and Stefan Blankenberg and Tanja Zeller and Peters, {James E} and Veikko Salomaa and Maria Fritsch and Ruth March and Aarno Palotie and Mark Daly and Butterworth, {Adam S} and Mervi Kinnunen and Paul, {Dirk S} and Athena Matakidou",
note = "{\textcopyright} 2022, Lemmel{\"a}, Wigmore et al.",
year = "2022",
month = aug,
day = "2",
doi = "10.7554/eLife.76272",
language = "English",
volume = "11",
journal = "ELIFE",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

RIS

TY - JOUR

T1 - Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans

AU - Lemmelä, Susanna

AU - Wigmore, Eleanor M

AU - Benner, Christian

AU - Havulinna, Aki S

AU - Ong, Rachel M Y

AU - Kempf, Tibor

AU - Wollert, Kai C

AU - Blankenberg, Stefan

AU - Zeller, Tanja

AU - Peters, James E

AU - Salomaa, Veikko

AU - Fritsch, Maria

AU - March, Ruth

AU - Palotie, Aarno

AU - Daly, Mark

AU - Butterworth, Adam S

AU - Kinnunen, Mervi

AU - Paul, Dirk S

AU - Matakidou, Athena

N1 - © 2022, Lemmelä, Wigmore et al.

PY - 2022/8/2

Y1 - 2022/8/2

N2 - Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in GDF15, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW pFDR = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.

AB - Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in GDF15, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW pFDR = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.

KW - Biomarkers

KW - Body Mass Index

KW - Cardiovascular Diseases/genetics

KW - Genome-Wide Association Study

KW - Humans

KW - Mendelian Randomization Analysis

U2 - 10.7554/eLife.76272

DO - 10.7554/eLife.76272

M3 - SCORING: Journal article

C2 - 35916366

VL - 11

JO - ELIFE

JF - ELIFE

SN - 2050-084X

M1 - e76272

ER -