对5000多名南亚人的血脂代谢物进行全基因组分析，揭示了心血管代谢疾病位点的生物学见解。
Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci.
作者信息
Harshfield Eric L, Fauman Eric B, Stacey David, Paul Dirk S, Ziemek Daniel, Ong Rachel M Y, Danesh John, Butterworth Adam S, Rasheed Asif, Sattar Taniya, Saleem Imran, Hina Zoubia, Ishtiaq Unzila, Qamar Nadeem, Mallick Nadeem Hayat, Yaqub Zia, Saghir Tahir, Rizvi Syed Nadeem Hasan, Memon Anis, Ishaq Mohammad, Rasheed Syed Zahed, Memon Fazal-Ur-Rehman, Jalal Anjum, Abbas Shahid, Frossard Philippe, Saleheen Danish, Wood Angela M, Griffin Julian L, Koulman Albert
机构信息
British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
出版信息
BMC Med. 2021 Sep 10;19(1):232. doi: 10.1186/s12916-021-02087-1.
BACKGROUND
Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies.
METHODS
We characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci.
RESULTS
We identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci.
CONCLUSIONS
Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.
背景
遗传、生活方式和环境因素可导致循环脂质水平紊乱，并增加心血管疾病和代谢性疾病的风险。然而，个体脂质种类的变化如何导致疾病风险往往并不明确。此外，在心血管研究中历史代表性不足的巴基斯坦人群中，脂质对心血管疾病的作用知之甚少。
方法
我们对来自巴基斯坦心肌梗死风险研究（PROMIS）的5662名医院对照者和来自INTERVAL研究的13814名健康英国献血者的人类血脂组遗传结构进行了表征。我们应用候选因果基因优先排序工具将与每种脂质相关的基因变异与最可能的因果基因联系起来，并使用高斯图形建模网络分析来识别和阐明脂质与基因位点之间的关系。
结果
我们在PROMIS中使用直接注入高分辨率质谱法测定的181种脂质中鉴定出253个遗传关联，在INTERVAL中与244种脂质鉴定出502个遗传关联。我们的分析揭示了与心脏代谢疾病相关基因位点的新生物学见解，包括在LPL、MBOAT7、LIPC、APOE-C1-C2-C4、SGPP1和SPTLC3基因位点的新型脂质关联。
结论
我们的研究结果是在一个研究较少的南亚人群中使用独特的脂质组学平台得出的，加强并扩展了脂质遗传决定因素及其与心脏代谢疾病相关基因位点关联的知识库。
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