School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
City University of New York, Graduate School of Public Health and Health Policy, New York, NY, USA.
Int J Epidemiol. 2023 Dec 25;52(6):1845-1852. doi: 10.1093/ije/dyad108.
Observationally, polyunsaturated fatty acids (PUFAs) have health benefits compared with saturated fatty acids (SFAs); randomized controlled trials suggest fewer benefits. We used uni- and multi-variable Mendelian randomization to assess the association of major fatty acids and their sub-species with ischaemic heart disease (IHD) overall and sex-specifically and with lifespan sex-specifically, given differing lifespan by sex.
We obtained strong (P <5x10-8), independent (r2<0.001) genetic predictors of fatty acids from genome-wide association studies (GWAS) in a random subset of 114 999 UK Biobank participants. We applied these genetic predictors to the Cardiogram IHD GWAS (cases = 60 801, controls = 123 504) and to the Finngen consortium GWAS (cases = 31 640, controls = 187 152) for replication and to the UK Biobank for sex-specific IHD and for lifespan based on parental attained age (fathers = 415 311, mothers = 412 937). We used sensitivity analysis and assessed sex differences where applicable.
PUFAs were associated with IHD [odds ratio 1.23, 95% confidence interval (CI) 1.05 to 1.44] and lifespan in men (-0.76 years, 95% CI -1.34 to -0.17) but not women (0.20, 95% CI -0.32 to 0.70). Findings were similar for omega-6 fatty acids and linoleic acid. Independent associations of SFAs, mono-unsaturated fatty acids or omega-3 fatty acids with IHD overall or lifespan in men and women were limited.
PUFAs, via specific subspecies, may contribute to disparities in lifespan by sex. Sex-specific dietary advice might be a start towards personalized public health and addressing inequities.
与饱和脂肪酸 (SFAs) 相比，多不饱和脂肪酸 (PUFAs) 在观察中具有健康益处；随机对照试验表明益处较少。我们使用单变量和多变量孟德尔随机化来评估主要脂肪酸及其亚种与整体缺血性心脏病 (IHD) 和性别特异性以及性别特异性寿命的关系，因为性别差异导致寿命不同。
我们从 114999 名英国生物库参与者的随机子集中获得了脂肪酸的强（P < 5x10-8）、独立（r2 < 0.001）遗传预测因子。我们将这些遗传预测因子应用于 Cardiogram IHD GWAS（病例= 60801，对照= 123504）和 Finngen 联盟 GWAS（病例= 31640，对照= 187152）进行复制，并应用于英国生物库进行性别特异性 IHD 和基于父母达到年龄的寿命（父亲= 415311，母亲= 412937）。我们使用敏感性分析并在适用的情况下评估了性别差异。
PUFAs 与 IHD 相关[比值比 1.23，95%置信区间 (CI) 1.05 至 1.44]和男性寿命（-0.76 岁，95%CI -1.34 至 -0.17），但与女性无关（0.20，95%CI -0.32 至 0.70）。omega-6 脂肪酸和亚油酸的发现也类似。SFAs、单不饱和脂肪酸或 omega-3 脂肪酸与男性和女性整体 IHD 或寿命的独立关联有限。
PUFAs 通过特定亚种可能导致性别间寿命差异。针对男性和女性的性别特异性饮食建议可能是迈向个性化公共卫生和解决不平等的起点。
