Associations between plasma fatty acid concentrations and schizophrenia: a two-sample Mendelian randomisation study

孟德尔随机化 脂肪酸 精神分裂症(面向对象编程) 医学 遗传学 生物 化学 基因 精神科 生物化学 遗传变异 基因型
作者
Hannah Jones,Maria Carolina Borges,Rebecca Carnegie,David Mongan,Peter J. Rogers,Sarah J. Lewis,Andrew Thompson,Stanley Zammit
出处
期刊:The Lancet Psychiatry [Elsevier]
卷期号:8 (12): 1062-1070 被引量:57
标识
DOI:10.1016/s2215-0366(21)00286-8
摘要

Although studies suggest that concentrations of omega-3 and omega-6 fatty acids are lower in individuals with schizophrenia, evidence for beneficial effects of fatty acid supplementation is scarce. Therefore, in this study, we aimed to determine whether omega-3 and omega-6 fatty acid concentrations are causally related to schizophrenia.We did a two-sample Mendelian randomisation study, using deidentified summary-level data that were publicly available. Exposure-outcome relationships were evaluated using the inverse variance weighted two-sample Mendelian randomisation method using results from genome-wide association studies (GWASs) of fatty acid concentrations and schizophrenia. GWAS results were available for European (fatty acids) and European and Asian (schizophrenia) ancestry samples. Overall age and gender information were not calculable from the summary-level GWAS results. Weighted median, weighted mode, and Mendelian randomisation Egger regression methods were used as sensitivity analyses. To address underlying mechanisms, further analyses were done using single instruments within the FADS gene cluster and ELOVL2 gene locus. FADS gene cluster and ELOVL2 gene causal effects on schizophrenia were calculated by dividing the single nucleotide polymorphism (SNP)-schizophrenia effect estimate by the SNP-fatty acid effect estimate with standard errors derived using the first term from a delta method expansion for the ratio estimate. Multivariable Mendelian randomisation was used to estimate direct effects of omega-3 fatty acids on schizophrenia, independent of omega-6 fatty acids, lipoproteins (ie, HDL and LDL), and triglycerides.Mendelian randomisation analyses indicated that long-chain omega-3 and long-chain omega-6 fatty acid concentrations were associated with a lower risk of schizophrenia (eg, inverse variance weighted odds ratio [OR] 0·83 [95% CI 0·75-0·92] for docosahexaenoic acid). By contrast, there was weak evidence that short-chain omega-3 and short-chain omega-6 fatty acids were associated with an increased risk of schizophrenia (eg, inverse variance weighted OR 1·07 [95% CI 0·98-1·18] for α-linolenic acid). Effects were consistent across the sensitivity analyses and the FADS single-SNP analyses, suggesting that long-chain omega-3 and long-chain omega-6 fatty acid concentrations were associated with lower risk of schizophrenia (eg, OR 0·74 [95% CI 0·58-0·96] for docosahexaenoic acid) whereas short-chain omega-3 and short-chain omega-6 fatty acid concentrations were associated with an increased risk of schizophrenia (eg, OR 1·08 [95% CI 1·02-1·15] for α-linolenic acid). By contrast, estimates from the ELOVL2 single-SNP analyses were more imprecise and compatible with both risk-increasing and protective effects for each of the fatty acid measures. Multivariable Mendelian randomisation indicated that the protective effect of docosahexaenoic acid on schizophrenia persisted after conditioning on other lipids, although evidence was slightly weaker (multivariable inverse variance weighted OR 0·84 [95% CI 0·71-1·01]).Our results are compatible with the protective effects of long-chain omega-3 and long-chain omega-6 fatty acids on schizophrenia, suggesting that people with schizophrenia might have difficulty converting short-chain polyunsaturated fatty acids to long-chain polyunsaturated fatty acids. Further studies are required to determine whether long-chain polyunsaturated fatty acid supplementation or diet enrichment might help prevent onset of schizophrenia.National Institute for Health Research Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
山260完成签到 ,获得积分10
刚刚
badada完成签到,获得积分10
刚刚
田様应助科研通管家采纳,获得10
2秒前
大模型应助科研通管家采纳,获得10
2秒前
科研通AI2S应助科研通管家采纳,获得10
2秒前
伶俐乐菱应助科研通管家采纳,获得10
3秒前
3秒前
3秒前
3秒前
shadow完成签到,获得积分10
4秒前
sen123完成签到,获得积分10
5秒前
123完成签到,获得积分20
6秒前
7秒前
NATURECATCHER完成签到,获得积分10
7秒前
温暖霸完成签到,获得积分10
7秒前
以筱完成签到,获得积分10
8秒前
NexusExplorer应助崔崔采纳,获得10
8秒前
CipherSage应助Passskd采纳,获得10
12秒前
13秒前
子睿完成签到,获得积分10
13秒前
背后雨柏完成签到 ,获得积分10
13秒前
14秒前
nanana发布了新的文献求助10
15秒前
量子星尘发布了新的文献求助10
15秒前
五月初夏完成签到,获得积分10
15秒前
hannah发布了新的文献求助10
18秒前
songvv完成签到,获得积分20
19秒前
哟哟哟完成签到,获得积分10
20秒前
20秒前
wanglejia完成签到,获得积分10
20秒前
从容的雪碧完成签到,获得积分10
20秒前
21秒前
Ac完成签到,获得积分10
21秒前
谦让的莆完成签到 ,获得积分10
21秒前
胡图图完成签到,获得积分0
21秒前
崔崔完成签到,获得积分10
22秒前
敖江风云完成签到,获得积分10
22秒前
浮生若梦完成签到 ,获得积分10
24秒前
Passskd发布了新的文献求助10
24秒前
杀出个黎明举报求助违规成功
24秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038235
求助须知:如何正确求助?哪些是违规求助? 3575992
关于积分的说明 11374009
捐赠科研通 3305760
什么是DOI,文献DOI怎么找? 1819276
邀请新用户注册赠送积分活动 892662
科研通“疑难数据库(出版商)”最低求助积分说明 815022