Using human genetics to understand the causes and consequences of circulating cardiac troponin I in the general population
Abstract Circulating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes is unclear. We combine data from the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study and perform a genome-wide association study of highsensitivity cTnI concentrations with 48 115 individuals.We identified 12 genetic loci (8 novel) associated with cTnI concentrations. Associated protein-altering variants highlighted putative functional genes:CAND2, HABP2, ANO5, APOH, FHOD3, TNFAIP2, KLKB1andLMAN1. Using two-sample Mendelian randomization we confirmed the non-causal role of cTnI in acute myocardial infarction, but could not rule out a causal role for cTnI in heart failure. Using genetically informed methods for causal inference of cTnI helps inform the role and value of measuring cTnI in the general population..
Medienart: |
Preprint |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
bioRxiv.org - (2022) vom: 16. Nov. Zur Gesamtaufnahme - year:2022 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Moksnes, Marta R [VerfasserIn] |
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Links: |
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Themen: |
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doi: |
10.1101/2020.09.04.20187401 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
XBI01869232X |
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520 | |a Abstract Circulating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes is unclear. We combine data from the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study and perform a genome-wide association study of highsensitivity cTnI concentrations with 48 115 individuals.We identified 12 genetic loci (8 novel) associated with cTnI concentrations. Associated protein-altering variants highlighted putative functional genes:CAND2, HABP2, ANO5, APOH, FHOD3, TNFAIP2, KLKB1andLMAN1. Using two-sample Mendelian randomization we confirmed the non-causal role of cTnI in acute myocardial infarction, but could not rule out a causal role for cTnI in heart failure. Using genetically informed methods for causal inference of cTnI helps inform the role and value of measuring cTnI in the general population. | ||
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