Genome-wide analyses of early-onset acute myocardial infarction identify 29 novel loci by whole genome sequencing

Jeon, Yeonsu; Jeon, Sungwon; Choi, Whan-Hyuk; An, Kyungwhan; Choi, Hansol; Kim, Byoung-Chul; Kim, Weon; Lee, Sang Yeob; Bae, Jang‐Whan; Hwang, Jin‐Yong; Kang, Min Gyu; Kim, Yeonkyung; Kang, Younghui; Kim, Yeo Jin; Kim, Byung Chul; Bhak, Jong; Shin, Eun‐Seok

doi:10.1007/s00439-022-02495-0

Cited by 3 publications

(7 citation statements)

References 53 publications

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“…These loci and their corresponding trait pairs were previously reported from chip-based GWAS summary results [ 31 , 32 ]. Similarly, we anticipate the fine-mapping analyses will also benefit from WGWAS, pinpointing novel genetic variants of phenotypic importance, as demonstrated in our prior work [ 33 ]. Taken together, whole genome sequencing with its genomic completeness should be a well-considered choice for future genomic association studies.…”

Section: Discussionmentioning

confidence: 93%

Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups

Jeon,

Choi,

Jeon

et al. 2024

GigaScience

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Background Phenome-wide association studies (PheWASs) have been conducted on Asian populations, including Koreans, but many were based on chip or exome genotyping data. Such studies have limitations regarding whole genome–wide association analysis, making it crucial to have genome-to-phenome association information with the largest possible whole genome and matched phenome data to conduct further population-genome studies and develop health care services based on population genomics. Results Here, we present 4,157 whole genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project. It encompasses most of the variants with allele frequency >0.001 in Koreans, indicating that it sufficiently covered most of the common and rare genetic variants with commonly measured phenotypes for Koreans. Korea4K provides 45,537,252 variants, and half of them were not present in Korea1K (1,094 samples). We also identified 1,356 new genotype–phenotype associations that were not found by the Korea1K dataset. Phenomics analyses further revealed 24 significant genetic correlations, 14 pleiotropic associations, and 127 causal relationships based on Mendelian randomization among 37 traits. In addition, the Korea4K imputation reference panel, the largest Korean variants reference to date, showed a superior imputation performance to Korea1K across all allele frequency categories. Conclusions Collectively, Korea4K provides not only the largest Korean genome data but also corresponding health check-up parameters and novel genome–phenome associations. The large-scale pathological whole genome–wide omics data will become a powerful set for genome–phenome level association studies to discover causal markers for the prediction and diagnosis of health conditions in future studies.

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Section: Discussionmentioning

confidence: 93%

Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups

Jeon,

Choi,

Jeon

et al. 2024

GigaScience

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“…Although rs78631167 did not show a strong association in the new cohort, rs8109584 showed a significant association with AMI ( P = 1.43 × 10 −5 ), which is 13 bp away from rs78631167, indicating that the genetic block where these variants lie may have a relationship with AMI. PLAUR encodes CD87, which converts plasminogen to plasmin, resulting in clot lysis and plaque healing ( 3 , 14 ).…”

Section: Resultsmentioning

confidence: 99%

“…A total of 1,173 patients with AMI from the Chungbuk National University Hospital in Korea were enrolled, and 1,747 healthy individuals from the Korean Genome Project (KGP) were selected as controls ( 5 , 6 ). Patients with AMI were hospitalized with a diagnosis of ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction caused by atherothrombotic occlusive lesions treated with PCI ( 3 , 7 ). Of the 1,173 patients with AMI, 88 and 1,085 were early-onset and late-onset patients, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Elucidating the genetic factors underlying AMI is complex, because environmental factors complicate the etiology of the disease ( 2 ). In our previous genome-wide association study (GWAS) ( 3 ), we had identified 29 novel genetic loci containing 85 suggestive variants of AMI by targeting 596 patients with early-onset AMI with a high genetic predisposition ( 4 ). This study provided evidence to support a genetic association between early-onset AMI and four biochemical pathways: thrombosis, fibrinolysis, inflammation, and lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

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Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortality

Jeon

Jeon²,

et al. 2023

Front. Cardiovasc. Med.

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BackgroundAcute myocardial infarction (AMI) is one of the leading causes of death worldwide, and approximately half of AMI-related deaths occur before the affected individual reaches the hospital. The present study aimed to identify and validate genetic variants associated with AMI and their role as prognostic markers.Materials and methodsWe conducted a replication study of 29 previously identified novel loci containing 85 genetic variants associated with early-onset AMI using a new independent set of 2,920 Koreans [88 patients with early- and 1,085 patients with late-onset AMI, who underwent percutaneous coronary intervention (PCI), and 1,747 healthy controls].ResultsOf the 85 previously reported early-onset variants, six were confirmed in our genome-wide association study with a false discovery rate of less than 0.05. Notably, rs12639023, a cis-eQTL located in the intergenic region between LINC02005 and CNTN3, significantly increased longitudinal cardiac mortality and recurrent AMI. CNTN3 is known to play a role in altering vascular permeability. Another variant, rs78631167, located upstream of PLAUR and known to function in fibrinolysis, was moderately replicated in this study. By surveying the nearby genomic region around rs78631167, we identified a significant novel locus (rs8109584) located 13 bp downstream of rs78631167. The present study showed that six of the early-onset variants of AMI are applicable to both early- and late-onset cases.ConclusionOur results confirm markers that can potentially be utilized to predict, screen, prevent, and treat candidate patients with AMI and highlight the potential of rs12639023 as a prognostic marker for cardiac mortality in AMI.

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“…Early-onset myocardial infarction, occurring before the age of 55 years, is more concerned now, 2 while the related genetic investigation of is far less than CHD. 1 , 5 , 6 …”

Section: Discussionmentioning

confidence: 99%

ACE Gene Mutations (rs577350502) in Early-Onset and Recurrent Myocardial Infarction: A Case Report and Review

Deng,

Guo,

Chen

et al. 2024

PGPM

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Background Acute myocardial infarction (AMI) is a severe acute coronary syndrome, demonstrating a trend toward affecting younger individuals in recent years. The association between early-onset myocardial infarction and single nucleotide polymorphism necessitates further exploration and evaluation. Case description We present a case of a patient experiencing early-onset and recurrent myocardial infarction. The patient underwent stent implantation for myocardial infarction at the age of 53 and subsequently encountered two more myocardial infarctions within a span of 16 years. Following interventional therapy, genetic testing was conducted to assess the efficacy of subsequent anti-heart failure medications, with the aim to preemptively address heart failure risks. Genetic testing revealed a mutation in the angiotensin-converting enzyme (ACE) gene (rs577350502, g.63488533C>A), characterized by an intron-deletion single nucleotide variant. Conclusion While this variant has not been previously reported to be associated with any specific disease, we hypothesize that it may contribute to the susceptibility and risk of myocardial infarction and coronary heart disease in the patient under consideration. This observation underscores the significance of investigating the insertion/deletion polymorphisms of the ACE gene in the context of AMI and emphasizes the necessity for further validation of this variant and other genetic markers associated with AMI in related diseases.

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Genome-wide analyses of early-onset acute myocardial infarction identify 29 novel loci by whole genome sequencing

Cited by 3 publications

References 53 publications

Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups

Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups

Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortality

ACE Gene Mutations (rs577350502) in Early-Onset and Recurrent Myocardial Infarction: A Case Report and Review

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