基因预测对红细胞和血浆多不饱和脂肪酸变化的影响。

IF 1.7 4区 医学 Q3 GENETICS & HEREDITY Genetic Epidemiology Pub Date : 2025-01-15 DOI:10.1002/gepi.22613
Nikhil K. Khankari, Timothy Su, Qiuyin Cai, Lili Liu, Elizabeth A. Jasper, Jacklyn N. Hellwege, Harvey J. Murff, Martha J. Shrubsole, Jirong Long, Todd L. Edwards, Wei Zheng
{"title":"基因预测对红细胞和血浆多不饱和脂肪酸变化的影响。","authors":"Nikhil K. Khankari,&nbsp;Timothy Su,&nbsp;Qiuyin Cai,&nbsp;Lili Liu,&nbsp;Elizabeth A. Jasper,&nbsp;Jacklyn N. Hellwege,&nbsp;Harvey J. Murff,&nbsp;Martha J. Shrubsole,&nbsp;Jirong Long,&nbsp;Todd L. Edwards,&nbsp;Wei Zheng","doi":"10.1002/gepi.22613","DOIUrl":null,"url":null,"abstract":"<p>Polyunsaturated fatty acids (PUFAs) including omega-3 and omega-6 are obtained from diet and can be measured objectively in plasma or red blood cells (RBCs) membrane biomarkers, representing different dietary exposure windows. In vivo conversion of omega-3 and omega-6 PUFAs from short- to long-chain counterparts occurs via a shared metabolic pathway involving fatty acid desaturases and elongase. This analysis leveraged genome-wide association study (GWAS) summary statistics for RBC and plasma PUFAs, along with expression quantitative trait loci (eQTL) to estimate tissue-specific genetically predicted gene expression effects for delta-5 desaturase (<i>FADS1</i>), delta-6 desaturase (<i>FADS2</i>), and elongase (<i>ELOVL2</i>) on changes in RBC and plasma biomarkers. Using colocalization, we identified shared variants associated with both increased gene expression and changes in RBC PUFA levels in relevant PUFA metabolism tissues (i.e., adipose, liver, muscle, and whole blood). We observed differences in RBC versus plasma PUFA levels for genetically predicted increase in <i>FADS1</i> and <i>FADS2</i> gene expression, primarily for omega-6 PUFAs linoleic acid (LA) and arachidonic acid (AA). The colocalization analysis identified rs102275 to be significantly associated with a 0.69% increase in total RBC membrane-bound LA levels (<i>p</i> = 5.4 × 10<sup>−12</sup>). Future PUFA genetic studies examining long-term PUFA biomarkers are needed to confirm our results.</p>","PeriodicalId":12710,"journal":{"name":"Genetic Epidemiology","volume":"49 1","pages":""},"PeriodicalIF":1.7000,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734643/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genetically Predicted Gene Expression Effects on Changes in Red Blood Cell and Plasma Polyunsaturated Fatty Acids\",\"authors\":\"Nikhil K. Khankari,&nbsp;Timothy Su,&nbsp;Qiuyin Cai,&nbsp;Lili Liu,&nbsp;Elizabeth A. Jasper,&nbsp;Jacklyn N. Hellwege,&nbsp;Harvey J. Murff,&nbsp;Martha J. Shrubsole,&nbsp;Jirong Long,&nbsp;Todd L. Edwards,&nbsp;Wei Zheng\",\"doi\":\"10.1002/gepi.22613\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Polyunsaturated fatty acids (PUFAs) including omega-3 and omega-6 are obtained from diet and can be measured objectively in plasma or red blood cells (RBCs) membrane biomarkers, representing different dietary exposure windows. In vivo conversion of omega-3 and omega-6 PUFAs from short- to long-chain counterparts occurs via a shared metabolic pathway involving fatty acid desaturases and elongase. This analysis leveraged genome-wide association study (GWAS) summary statistics for RBC and plasma PUFAs, along with expression quantitative trait loci (eQTL) to estimate tissue-specific genetically predicted gene expression effects for delta-5 desaturase (<i>FADS1</i>), delta-6 desaturase (<i>FADS2</i>), and elongase (<i>ELOVL2</i>) on changes in RBC and plasma biomarkers. Using colocalization, we identified shared variants associated with both increased gene expression and changes in RBC PUFA levels in relevant PUFA metabolism tissues (i.e., adipose, liver, muscle, and whole blood). We observed differences in RBC versus plasma PUFA levels for genetically predicted increase in <i>FADS1</i> and <i>FADS2</i> gene expression, primarily for omega-6 PUFAs linoleic acid (LA) and arachidonic acid (AA). The colocalization analysis identified rs102275 to be significantly associated with a 0.69% increase in total RBC membrane-bound LA levels (<i>p</i> = 5.4 × 10<sup>−12</sup>). Future PUFA genetic studies examining long-term PUFA biomarkers are needed to confirm our results.</p>\",\"PeriodicalId\":12710,\"journal\":{\"name\":\"Genetic Epidemiology\",\"volume\":\"49 1\",\"pages\":\"\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-01-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734643/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genetic Epidemiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/gepi.22613\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetic Epidemiology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/gepi.22613","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

摘要

包括omega-3和omega-6在内的多不饱和脂肪酸(PUFAs)可以从饮食中获得,并且可以在血浆或红细胞(rbc)膜生物标志物中客观测量,代表不同的饮食暴露窗口。体内omega-3和omega-6 PUFAs从短链到长链的转化是通过脂肪酸去饱和酶和延长酶的共同代谢途径进行的。该分析利用全基因组关联研究(GWAS)对红细胞和血浆PUFAs的汇总统计数据,以及表达数量性状位点(eQTL)来估计δ -5去饱和酶(FADS1)、δ -6去饱和酶(FADS2)和延长酶(ELOVL2)对红细胞和血浆生物标志物变化的组织特异性遗传预测基因表达效应。通过共定位,我们确定了与相关PUFA代谢组织(即脂肪、肝脏、肌肉和全血)中基因表达增加和RBC PUFA水平变化相关的共享变异。我们观察到红细胞与血浆PUFA水平的差异,基因预测FADS1和FADS2基因表达的增加,主要是omega-6 PUFA亚油酸(LA)和花生四烯酸(AA)。共定位分析发现rs102275与红细胞膜结合LA总水平增加0.69%显著相关(p = 5.4 × 10-12)。未来的PUFA基因研究需要检测长期PUFA生物标志物来证实我们的结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Genetically Predicted Gene Expression Effects on Changes in Red Blood Cell and Plasma Polyunsaturated Fatty Acids

Polyunsaturated fatty acids (PUFAs) including omega-3 and omega-6 are obtained from diet and can be measured objectively in plasma or red blood cells (RBCs) membrane biomarkers, representing different dietary exposure windows. In vivo conversion of omega-3 and omega-6 PUFAs from short- to long-chain counterparts occurs via a shared metabolic pathway involving fatty acid desaturases and elongase. This analysis leveraged genome-wide association study (GWAS) summary statistics for RBC and plasma PUFAs, along with expression quantitative trait loci (eQTL) to estimate tissue-specific genetically predicted gene expression effects for delta-5 desaturase (FADS1), delta-6 desaturase (FADS2), and elongase (ELOVL2) on changes in RBC and plasma biomarkers. Using colocalization, we identified shared variants associated with both increased gene expression and changes in RBC PUFA levels in relevant PUFA metabolism tissues (i.e., adipose, liver, muscle, and whole blood). We observed differences in RBC versus plasma PUFA levels for genetically predicted increase in FADS1 and FADS2 gene expression, primarily for omega-6 PUFAs linoleic acid (LA) and arachidonic acid (AA). The colocalization analysis identified rs102275 to be significantly associated with a 0.69% increase in total RBC membrane-bound LA levels (p = 5.4 × 10−12). Future PUFA genetic studies examining long-term PUFA biomarkers are needed to confirm our results.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Genetic Epidemiology
Genetic Epidemiology 医学-公共卫生、环境卫生与职业卫生
CiteScore
4.40
自引率
9.50%
发文量
49
审稿时长
6-12 weeks
期刊介绍: Genetic Epidemiology is a peer-reviewed journal for discussion of research on the genetic causes of the distribution of human traits in families and populations. Emphasis is placed on the relative contribution of genetic and environmental factors to human disease as revealed by genetic, epidemiological, and biologic investigations. Genetic Epidemiology primarily publishes papers in statistical genetics, a research field that is primarily concerned with development of statistical, bioinformatical, and computational models for analyzing genetic data. Incorporation of underlying biology and population genetics into conceptual models is favored. The Journal seeks original articles comprising either applied research or innovative statistical, mathematical, computational, or genomic methodologies that advance studies in genetic epidemiology. Other types of reports are encouraged, such as letters to the editor, topic reviews, and perspectives from other fields of research that will likely enrich the field of genetic epidemiology.
期刊最新文献
Dimension Reduction Using Local Principal Components for Regression-Based Multi-SNP Analysis in 1000 Genomes and the Canadian Longitudinal Study on Aging (CLSA) Issue Information Sex-Specific Association Between Polymorphisms in Estrogen Receptor Alpha Gene (ESR1) and Depression: A Genome-Wide Association Study of All of Us and UK Biobank Data Reference-Based Standardization Approach Stabilizing Small Batch Risk Prediction via Polygenic Score Issue Information
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1