Genome-wide association analysis of plasma lipidome identifies 495 genetic associations

Ottensmann, Linda; Tabassum, Rubina; Ruotsalainen, Sanni; Gerl, Mathias J.; Klose, Christian; Widén, Elisabeth; Simons, Kai; Ripatti, Samuli; Pirinen, Matti

doi:10.1101/2023.01.21.23284765

Cited by 13 publications

(16 citation statements)

References 79 publications

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“…DEPICT analyses were conducted using suggestively significant SNVs ( P < 1 × 10 −5 ). Gene-set enrichment (eTable 3 in the Supplement) and tissue enrichment (eTable 4 in the Supplement) analyses showed some biologically relevant tissues among the top hits, including heart valve tissue; however, these results were not significant after adjustment for multiple hypothesis testing (false-discovery rate P < .05) …”

Section: Resultsmentioning

confidence: 99%

Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals

et al. 2021

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IMPORTANCE Rheumatic heart disease (RHD), a sequela of rheumatic fever characterized by permanent heart valve damage, is the leading cause of cardiac surgery in Africa. However, its pathophysiologic characteristics and genetics are poorly understood. Understanding genetic susceptibility may aid in prevention, control, and interventions to eliminate RHD. OBJECTIVE To identify common genetic loci associated with RHD susceptibility in Black African individuals. DESIGN, SETTING, AND PARTICIPANTSThis multicenter case-control genome-wide association study (GWAS), the Genetics of Rheumatic Heart Disease, examined more than 7 million genotyped and imputed single-nucleotide variations. The 4809 GWAS participants and 116 independent trio families were enrolled from 8 African countries between

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Section: Resultsmentioning

confidence: 99%

Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals

et al. 2021

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“…The relevant GWAS results are accessible via a comprehensive catalog ranging from GCST90277238 to GCST90277287. This extensive dataset offered a diverse and in-depth analysis of lipid species and their potential genetic associations with health outcomes [15].…”

Section: Lipidomic Gwas Data Sourcesmentioning

confidence: 99%

Unraveling the Genetic Links Between Plasma Lipidome and Ankylosing Spondylitis: Insights from a Two-Sample Mendelian Randomization Approach

Wu,

Wei,

Ding

et al. 2024

Preprint

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Background: Emerging epidemiological evidence indicates an association between Plasma Lipidome and Ankylosing Spondylitis (AS), yet our grasp of the underlying genetic and causative links remains nascent. This study endeavors to unravel the genetic interplay and assess the causality within this association. Methods: This investigation utilized a two-sample Mendelian Randomization (MR) technique to discern the causal dynamics between lipid profiles and AS. To ascertain causal relationships among 179 distinct lipid molecules and AS susceptibility, we capitalized on extensive GWAS data. The primary analytical tool was the inverse variance weighted (IVW) method, complemented by MR Egger, weighted median, Weighted mode, and Simple mode analyses to ensure comprehensiveness. To assess result consistency, the Cochrane Q-test gauged heterogeneity and the MR-Egger intercept test, alongside MR-PRESSO, scrutinized for horizontal pleiotropy. Lastly, a leave-one-out sensitivity analysis authenticated the findings' stability. Results: The results indicated that levels of Sterol ester (27:1/18:0), Sterol ester (27:1/18:2), Phosphatidylethanolamine (18:1_0:0), Phosphatidylcholine (16:1_18:1), Phosphatidylcholine (16:1_20:4), Phosphatidylcholine (17:0_18:2), Phosphatidylcholine (18:0_20:3), Phosphatidylcholine (18:0_22:6), Phosphatidylcholine (O-16:0_20:4), Phosphatidylcholine (O-18:1_18:2), Phosphatidylinositol (18:1_18:2), Triacylglycerol (50:3), Triacylglycerol (54:3), and Triacylglycerol (56:8) were genetically predicted as consequences of AS. There was no evidence of horizontal pleiotropy or heterogeneity between the genetic variants (P>0.05), and a leave-one-out test confirmed the stability and robustness of this association. Conclusion: Our study deepens the understanding of the genetic research into the close connection between lipid levels and AS, providing guidance for future clinical and basic research.

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“…Regarding the exposure factor, we utilized the recent genetic study on the plasma lipidome of 7174 Finnish individuals, which included 179 lipid species [14]. We conducted MR analysis using the genome-wide association study (GWAS) IDs (GCST90277238-GCST90277416) provided by the authors.…”

Section: Data Sources For Exposure and Outcome Datamentioning

confidence: 99%

Causal Relationship Between Plasma Lipidome and Six Types of Cancer: A Mendelian Randomization Study

Tang,

Zhang,

Yang

et al. 2024

Preprint

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Background: The plasma lipidome is intricately associated with cancer. However, the causal relationship between them remains uncertain. Therefore, this study employs Mendelian randomization (MR) based on genetic principles to investigate the potential causal relationship between plasma lipidome and six common types of cancer. Methods: MR analysis utilizes publicly available genetic data, employing a genome-wide association study (GWAS) of 179 lipid species as exposure and GWAS datasets of six different cancers as outcomes. The inverse variance weighted (IVW) method serves as the primary approach, with MR-Egger regression and weighted median (WM) method employed as supplementary methods for analysis. Additionally, sensitivity analyses including Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis are conducted to assess the reliability and stability of causal relationships. The Steiger test is also utilized to determine the directionality of causal relationships. Results: The IVW analysis reveals that phosphatidylethanolamine (16:0_20:4) levels and others are implicated as risk factors for hepatic cancer, while sphingomyelin (d40:1) levels and others are identified as protective factors against hepatic cancer. Sterol ester (27:1/20:4) levels and others are associated with increased risk of lung cancer, whereas sterol ester (27:1/18:2) levels and others are associated with decreased risk of lung cancer. Sterol ester (27:1/20:3) levels and others are identified as risk factors for colorectal cancer, whereas phosphatidylcholine (18:2_0:0) levels and others are protective against colorectal cancer. Phosphatidylcholine (16:0_20:4) levels and others are linked to increased risk of esophageal cancer, while phosphatidylcholine (16:0_18:3) levels and others are associated with protection against esophageal cancer. Phosphatidylinositol (18:0_20:4) levels and others are identified as risk factors for thyroid cancer, whereas phosphatidylinositol (16:0_18:2) levels and others are protective against thyroid cancer. Diacylglycerol (18:1_18:2) levels and others are identified as protective factors against breast cancer. Conclusions: There exists a clear causal relationship between plasma lipidome and six types of cancer. Additionally, it has been observed that the same single-nucleotide polymorphisms (SNPs) serve as instrumental variables (IVs), influencing cancer through the plasma lipidome. This provides further avenues and methodologies for early screening and effective treatment of cancer.

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Genome-wide association analysis of plasma lipidome identifies 495 genetic associations

Cited by 13 publications

References 79 publications

Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals

Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals

Unraveling the Genetic Links Between Plasma Lipidome and Ankylosing Spondylitis: Insights from a Two-Sample Mendelian Randomization Approach

Causal Relationship Between Plasma Lipidome and Six Types of Cancer: A Mendelian Randomization Study

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