Traore Mariam, Sangare Harouna, Diabate Oudou, Diawara Abdoulaye, Cissé Cheickna, Nashiru Oyekanmi, Li Jian, Shaffer Jeffrey, Wélé Mamadou, Doumbia Seydou, Chikowore Tinashe, Soremekun Opeyemi, Fatumo Segun
The African Computational Genomics (TACG) Research Group, Medical Research Council /Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
African Center of Excellence in Bioinformatics, University of Sciences, Techniques and Technologies of Bamako, Bamako, Mali.
Ann Hum Genet. 2025 Jul;89(4):178-187. doi: 10.1111/ahg.12555. Epub 2024 Mar 15.
Dyslipidemia is becoming prevalent in Africa, where malaria is endemic. Observational studies have documented the long-term protective effect of malaria on dyslipidemia; however, these study designs are prone to confounding. Therefore, we used Mendelian randomization (MR, a method robust to confounders and reverse causation) to determine the causal effect of severe malaria (SM) and the recurrence of non-severe malaria (RNM) on lipid traits.
We performed two-sample MR using genome wide association study (GWAS) summary statistics for recurrent non-severe malaria (RNM) from a Benin cohort (N = 775) and severe malaria from the MalariaGEN dataset (N = 17,000) and lipid traits from summary-level data of a meta-analyzed African lipid GWAS (MALG, N = 24,215) from the African Partnership for Chronic Disease Research (APCDR) (N = 13,612) and the Africa Wits-IN-DEPTH partnership for genomics studies (AWI-Gen) dataset (N = 10,603).
No evidence of significant causal association was obtained between RNM and high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglycerides. However, a notable association emerged between severe malarial anaemia (SMA) which is a subtype of severe malaria and reduced HDL-C levels, suggesting a potential subtype-specific effect. Nonetheless, we strongly believe that the small sample size likely affects our estimates, warranting cautious interpretation of these results.
Our findings challenge the hypothesis of a broad causal relationship between malaria (both severe and recurrent non-severe forms) and dyslipidemia. The isolated association with SMA highlights an intriguing area for future research. However, we believe that conducting larger studies to investigate the connection between malaria and dyslipidemia in Africa will enhance our ability to better address the burden posed by both diseases.
血脂异常在疟疾流行的非洲正变得普遍。观察性研究已记录了疟疾对血脂异常的长期保护作用；然而，这些研究设计容易受到混杂因素的影响。因此，我们使用孟德尔随机化（MR，一种对混杂因素和反向因果关系具有稳健性的方法）来确定重症疟疾（SM）和非重症疟疾复发（RNM）对血脂特征的因果效应。
我们使用来自贝宁队列（N = 775）的复发性非重症疟疾（RNM）、疟疾基因组数据集（N = 17,000）中的重症疟疾以及来自非洲慢性病研究伙伴关系（APCDR）（N = 13,612）和非洲维茨深度基因组学研究伙伴关系（AWI-Gen）数据集（N = 10,603）的荟萃分析非洲脂质全基因组关联研究（MALG，N = 24,215）的汇总水平数据中的血脂特征，进行了两样本MR分析。
未获得RNM与高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、总胆固醇和甘油三酯之间存在显著因果关联的证据。然而，重症疟疾的一种亚型——重症疟疾病毒性贫血（SMA）与HDL-C水平降低之间出现了显著关联，表明存在潜在的亚型特异性效应。尽管如此，我们坚信小样本量可能影响了我们的估计，因此对这些结果的解释需谨慎。
我们的研究结果对疟疾（包括重症和复发性非重症形式）与血脂异常之间广泛因果关系的假设提出了挑战。与SMA的孤立关联突出了一个有趣的未来研究领域。然而，我们认为开展更大规模的研究以调查非洲疟疾与血脂异常之间的联系，将提高我们更好应对这两种疾病所带来负担的能力。
