Annals of Human Genetics最新文献

{"title":"Epithelial–mesenchymal transition dysregulation in prostate cancer: Insights from molecular unraveling and epidemiological analyses in Tunisia, North Africa","authors":"Rahma Said,&nbsp;Javier Hernández-Losa,&nbsp;Rosa Somoza Lopez de Haro,&nbsp;Teresa Moline,&nbsp;Skander Zouari,&nbsp;Ahlem Blel,&nbsp;Soumaya Rammeh,&nbsp;Amine Derouiche,&nbsp;Slah Ouerhani","doi":"10.1111/ahg.12563","DOIUrl":"10.1111/ahg.12563","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The progression of prostate cancer (PCa) has been linked worldwide, including in African populations, to the dysregulation of the epithelial–mesenchymal transition (EMT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To clarify the connection among EMT markers, clinicopathological parameters, and epidemiological factors, we analyzed 35 PCa specimens from patients in Tunisia, a country in North Africa, arranged by stages. We also carried out extensive molecular and epidemiological analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant dysregulation of EMT genes was found, with an overexpression of <i>ZEB-1</i>, <i>Twist</i>, <i>Snail-1</i>, and <i>Vimentin</i> (<i>p</i> &lt; 0.05) and underexpression of <i>E-cadherin</i> and <i>β-catenin</i> (<i>p &lt;</i> 0.05). Positive correlations were observed between transcription factors and the mesenchymal marker <i>Vimentin</i> (<i>p</i> &lt; 0.001, <i>r</i> = 0.574; <i>p</i> = 0.029, <i>r</i> = 0.411; and <i>p</i> &lt; 0.001; <i>r</i> = 0.506) according to Spearman correlation analyses, whereas negative correlations were found between epithelial markers (<i>E-cadherin, β-catenin</i>) and <i>Vimentin</i> (<i>p</i> &lt; 0.05; <i>r</i> &lt; 0). Higher PSA, Gleason scores, and metastasis were all correlated with the dysregulation of EMT (<i>p</i> &lt; 0.05). Notably, there was a positive correlation between higher consumption of tobacco (≥20 Packets per year) and <i>Vimentin</i> expression (<i>p</i> &lt; 0.001, <i>r</i> = 0.854), suggesting a relationship between smoking and EMT activation in the Tunisian population. Moreover, <i>Twist</i> showed a positive correlation with diabetes (<i>p</i> &lt; 0.001, <i>r</i> = 0.385), whereas no significant correlations were found between EMT markers and comorbidities such as hypertension and coronary insufficiency. These results demonstrate the intricate connection between molecular changes, epidemiological factors, and disease progression, and they emphasize the crucial role that EMT plays in promoting PCa aggressiveness in African populations, particularly in Tunisia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, understanding these correlations could help develop focused treatment plans and enhance patient outcomes for PCa management in African settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 4","pages":"169-177"},"PeriodicalIF":1.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attention-deficit/hyperactivity disorder and dopamine receptor D4 (DRD4) exon 3 variable number of tandem repeats (VNTR) 2-repeat allele","authors":"Larry Baum,&nbsp;Chi Chiu Lee,&nbsp;Rui Ye,&nbsp;Yuanxin Zhong,&nbsp;Se Fong Hung,&nbsp;Chun Pan Tang,&nbsp;Ting Pong Ho,&nbsp;James M Swanson,&nbsp;Robert K Moyzis,&nbsp;Pak-Chung Sham,&nbsp;Patrick Wing-Leung Leung","doi":"10.1111/ahg.12560","DOIUrl":"10.1111/ahg.12560","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>To investigate the association of attention-deficit/hyperactivity disorder (ADHD) with the 48-base pair (bp) variable number of tandem repeats (VNTR) in exon 3 of the dopamine receptor D4 (DRD4) gene, we genotyped 240 ADHD patients and their parents from Hong Kong. The 4R allele was most common, followed by 2R. We examined association between the 2R allele (relative to 4R) and ADHD by Transmission Disequilibrium Test (TDT). The odds ratio (OR) (95% confidence interval) was 0.90 (0.64–1.3). The <i>p</i>-value was 0.6. Examining subgroups revealed nominally significant association of 2R with inattentive ADHD: OR = 0.33 (0.12–0.92) and <i>p</i> = 0.03. Because our study used TDT analysis, we meta-analyzed the association of 2R with ADHD in Asians (1329 patient alleles), revealing results similar to ours: OR = 0.97 (0.80–1.2) and <i>p</i> = 0.8. To examine the association of 2R with inattentive ADHD, we meta-analyzed all studies (regardless of analysis type or ethnicity, in order to increase statistical power): 702 patient alleles, 1420 control alleles, OR = 0.81 (0.57–1.1) and <i>p</i> = 0.2. Overall, there is no evidence of association between ADHD and the 2R allele, but the suggestive association with the inattentive type warrants further investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 5","pages":"382-391"},"PeriodicalIF":1.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12560","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variations in CYP2A6, CYP2E1, GSTM1, GSTT1 genes and the risk of Nasopharyngeal carcinoma in North African population","authors":"Imane EL Alami,&nbsp;Wafa Khaali,&nbsp;Majida Jalbout,&nbsp;Amina Gihbid,&nbsp;Wided Ben Ayoub,&nbsp;Abdellatif Benider,&nbsp;Selma Mohamed Brahim,&nbsp;Mokhtar Hamdi Cherif,&nbsp;Nadia Benchakroun,&nbsp;Mohammed El Mzibri,&nbsp;El Khalil Ben Driss,&nbsp;Khalid Belghmi,&nbsp;Marilys Corbex,&nbsp;Meriem Khyatti","doi":"10.1111/ahg.12562","DOIUrl":"10.1111/ahg.12562","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy associated with both genetic and environmental factors. Polymorphic deletions of the phase I and phase II genes involved in the detoxification of potential carcinogens may be a risk factor for nasopharyngeal carcinoma. In this study, we investigated the relationship between <i>CYP2E1</i> (rs3813867), <i>CYP2A6, GSTM1</i>(rs1183423000) and <i>GSTT1</i>(rs1601993659) gene variations and NPC risk in North African countries with the highest incidence of NPC (Morocco, Algeria and Tunisia). and the evaluation of the potential use of these variants as potential biomarkers for NPC management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 600 NPC cases and 545 controls frequency-matched on ethnicity, sex, age and childhood household type, were recruited from three North African countries (Morocco, Algeria and Tunisia) and analysed. Genotyping of <i>CYP2A6</i> and <i>CYP2E1</i>(rs3813867) was performed by polymerase chain reaction restriction (PCR)-fragment length polymorphism (RFLP) analysis and the <i>GSTM1</i> (rs1183423000) and <i>GSTT1</i>(rs1601993659) genetic variations were evaluated using the PCR technique.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The genotype distributions of <i>CYP2E1</i>(rs3813867)<i>, CYP2A6, GSTM1</i>(rs1183423000) and <i>GSTT1</i>(rs1601993659) genotypes did not differ significantly among NPC cases and controls (<i>p</i> &gt; 0.05). Furthermore, our data did not reveal any association with smoking and the studied variants, even when the samples were stratified by the duration period of smoking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this large studied North African population, our findings suggest that the functional <i>CYP2E1</i>, <i>CYP2A6, GSTM1</i> and <i>GSTT1</i> variations did not influence NPC susceptibility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 4","pages":"158-168"},"PeriodicalIF":1.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Need of the hour? Genetic and genomic testing referrals from primary healthcare centers with inclusion of precision medicine in Pakistan","authors":"Muhammad Osama Siddiqui,&nbsp;Rabeet Tariq,&nbsp;Raman Kumar,&nbsp;Saira Mansoor","doi":"10.1111/ahg.12561","DOIUrl":"10.1111/ahg.12561","url":null,"abstract":"","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 6","pages":"399-401"},"PeriodicalIF":1.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140608475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A historical perspective on Lionel Penrose: Scientist, geneticist and dedicated opponent of eugenics","authors":"Maria Kiladi","doi":"10.1111/ahg.12551","DOIUrl":"https://doi.org/10.1111/ahg.12551","url":null,"abstract":"The paper explores Lionel Penrose's scientific work. Penrose investigated the causes of mental disorders from clinical and genetic points of view. His investigations on phenylketonuria and Down syndrome helped to demonstrate the heterogenous character of mental disorders, whose causes can range from genetic with high penetrance, to largely environmental. He was specifically selected by JBS Haldane to become University College London's third Galton Chair as a result of his Colchester survey investigations. He became the first Galton Chair who had medical training. He never concealed his distaste for anything related to eugenics. As well as using his scientific work to reject eugenic ideas such as suggestions on sterilisation measures or the existence of a social problem group, he campaigned successfully to rename the Department of Eugenics, Biometry and Genetics to Department of Human Genetics and Biometry. With his work, he discredited prejudiced eugenic ideas on mental disorders and became an advocate for those with mental disabilities.","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"16 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An exploration of the genetics of the mutant Huntingtin (mHtt) gene in a cohort of patients with chorea from different ethnic groups in sub-Saharan Africa","authors":"Mendi J Muthinja,&nbsp;Carlos Othon Guelngar,&nbsp;Maouly Fall,&nbsp;Fatumah Jama,&nbsp;Huda Aldeen Shuja,&nbsp;Jamila Nambafu,&nbsp;Daniel Gams Massi,&nbsp;Oluwadamilola O. Ojo,&nbsp;Njideka U. Okubadejo,&nbsp;Funmilola Tolulope Taiwo,&nbsp;Alassane Mamadou Diop,&nbsp;Coudjou J. D. G. de Chacus,&nbsp;Fodé Abass Cissé,&nbsp;Amara Cissé,&nbsp;Juzar Hooker,&nbsp;Dilraj Sokhi,&nbsp;Henry Houlden,&nbsp;Mie Rizig","doi":"10.1111/ahg.12557","DOIUrl":"10.1111/ahg.12557","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Africans are underrepresented in Huntington's disease (HD) research. A European ancestor was postulated to have introduced the mutant &lt;i&gt;Huntingtin&lt;/i&gt; (&lt;i&gt;mHtt&lt;/i&gt;) gene to the continent; however, recent work has shown the existence of a unique &lt;i&gt;Htt&lt;/i&gt; haplotype in South-Africa specific to indigenous Africans.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We aimed to investigate the CAG trinucleotide repeats expansion in the &lt;i&gt;Htt&lt;/i&gt; gene in a geographically diverse cohort of patients with chorea and unaffected controls from sub-Saharan Africa.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We evaluated 99 participants: 43 patients with chorea, 21 asymptomatic first-degree relatives of subjects with chorea, and 35 healthy controls for the presence of the &lt;i&gt;mHtt&lt;/i&gt;. Participants were recruited from 5 African countries. Additional data were collected from patients positive for the &lt;i&gt;mHtt&lt;/i&gt; gene; these included demographics, the presence of psychiatric and (or) cognitive symptoms, family history, spoken languages, and ethnic origin. Additionally, their pedigrees were examined to estimate the number of people at risk of developing HD and to trace back the earliest account of the disease in each region.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;HD cases were identified in all countries. Overall, 53.4% of patients with chorea were carriers for the &lt;i&gt;mHTT&lt;/i&gt;; median tract size was 45 CAG repeats. Of the asymptomatic relatives, 28.6% (6/21) were carriers for the &lt;i&gt;mHTT;&lt;/i&gt; median tract size was 40 CAG. No homozygous carries were identified. Median CAG tract size in controls was 17 CAG repeats. Men and women were equally affected by HD. All patients with HD—bar three who were juvenile onset of &lt;21 years—were defined as adult onset (median age of onset was 40 years). HD transmission followed an autosomal dominant pattern in 84.2% (16/19) of HD families. In familial cases, maternal transmission was higher 52.6% (10/19) than paternal transmission 36.8% (7/19). The number of asymptomatic individuals at risk of developing HD was estimated at ten times more than the symptomatic patients. HD could be traced back to the early 1900s in most African sites. HD cases spread over seven ethnic groups belonging to two distinct linguistic lineages separated from each other approximately 54–16 kya ago: Nilo-Sahara and Niger-Congo.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This is the first study examining","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 4","pages":"149-157"},"PeriodicalIF":1.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12557","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review and research gap identification in genetics causes of syndromic and nonsyndromic hearing loss in Saudi Arabia","authors":"Faisal Almalki","doi":"10.1111/ahg.12559","DOIUrl":"10.1111/ahg.12559","url":null,"abstract":"<p>Congenital hearing loss is one of the most common sensory disabilities worldwide. The genetic causes of hearing loss account for 50% of hearing loss. Genetic causes of hearing loss can be classified as nonsyndromic hearing loss (NSHL) or syndromic hearing loss (SHL). NSHL is defined as a partial or complete hearing loss without additional phenotypes; however, SHL, known as hearing loss, is associated with other phenotypes. Both types follow a simple Mendelian inheritance fashion. Several studies have been conducted to uncover the genetic factors contributing to NSHL and SHL in Saudi patients. However, these studies have encountered certain limitations. This review assesses and discusses the genetic factors underpinning NSHL and SHL globally, with a specific emphasis on the Saudi Arabian context. It also explores the prevalence of the most observed genetic causes of NSHL and SHL in Saudi Arabia. It also sheds light on areas where further research is needed to fully understand the genetic foundations of hearing loss in the Saudi population. This review identifies several gaps in research in NSHL and SHL and provides insights into potential research to be conducted.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 5","pages":"364-381"},"PeriodicalIF":1.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12559","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dawn of a cure for sickle cell disease through CRISPR-based treatment: A critical test of equity in public health genomics","authors":"Gerald Mboowa,&nbsp;Ivan Sserwadda,&nbsp;Stephen Kanyerezi,&nbsp;Stephen Tukwasibwe,&nbsp;Benson Kidenya","doi":"10.1111/ahg.12558","DOIUrl":"10.1111/ahg.12558","url":null,"abstract":"<p>Equity in access to genomic technologies, resources, and products remains a great challenge. This was evident especially during the coronavirus disease 2019 (COVID-19) pandemic when the majority of lower middle-income countries were unable to achieve at least 10% population vaccination coverage during initial COVID-19 vaccine rollouts, despite the rapid development of those vaccines. Sickle cell disease (SCD) is an inherited monogenic red blood cell disorder that affects hemoglobin, the protein that carries oxygen through the body. Globally, the African continent carries the highest burden of SCD with at least 240,000 children born each year with the disease. SCD has evolved from a treatable to a curable disease. Recently, the UK medical regulator approved its cure through clustered regularly interspaced short palindromic repeat (CRISPR)-based treatment, whereas the US Food and Drug Administration has equally approved two SCD gene therapies. This presents a remarkable opportunity to demonstrate equity in public health genomics. This CRISPR-based treatment is expensive and therefore, a need for an ambitious action to ensure that they are affordable and accessible where they are needed most and stand to save millions of lives.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 4","pages":"188-194"},"PeriodicalIF":1.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Drosophila amyloid toxicity models to study Alzheimer's disease","authors":"Elli Tsintzas,&nbsp;Teresa Niccoli","doi":"10.1111/ahg.12554","DOIUrl":"10.1111/ahg.12554","url":null,"abstract":"<p>Alzheimer's disease (AD) is the most prevalent form of dementia and is characterised by a progressive loss of neurons, which manifests as gradual memory decline, followed by cognitive loss. Despite the significant progress in identifying novel biomarkers and understanding the prodromal pathology and symptomatology, AD remains a significant unmet clinical need. Lecanemab and aducanumab, the only Food and Drug Administration approved drugs to exhibit some disease-modifying clinical efficacy, target Aβ amyloid, underscoring the importance of this protein in disease aetiology. Nevertheless, in the absence of a definitive cure, the utilisation of preclinical models remains imperative for the identification of novel therapeutic targets and the evaluation of potential therapeutic agents. <i>Drosophila melanogaster</i> is a model system that can be used as a research tool to investigate neurodegeneration and therapeutic interventions. The short lifespan, low price and ease of husbandry/rearing make <i>Drosophila</i> an advantageous model organism from a practical perspective. However, it is the highly conserved genome and similarity of <i>Drosophila</i> and human neurobiology which make flies a powerful tool to investigate neurodegenerative mechanisms. In addition, the ease of transgenic modifications allows for early proof of principle studies for future therapeutic approaches in neurodegenerative research. This mini review will specifically focus on utilising <i>Drosophila</i> as an in vivo model of amyloid toxicity in AD.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 5","pages":"349-363"},"PeriodicalIF":1.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12554","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal effect of severe and non-severe malaria on dyslipidemia in African Ancestry individuals: A Mendelian randomization study","authors":"Mariam Traore,&nbsp;Harouna Sangare,&nbsp;Oudou Diabate,&nbsp;Abdoulaye Diawara,&nbsp;Cheickna Cissé,&nbsp;Oyekanmi Nashiru,&nbsp;Jian Li,&nbsp;Jeffrey Shaffer,&nbsp;Mamadou Wélé,&nbsp;Seydou Doumbia,&nbsp;Tinashe Chikowore,&nbsp;Opeyemi Soremekun,&nbsp;Segun Fatumo","doi":"10.1111/ahg.12555","DOIUrl":"10.1111/ahg.12555","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We performed two-sample MR using genome wide association study (GWAS) summary statistics for recurrent non-severe malaria (RNM) from a Benin cohort (<i>N</i> = 775) and severe malaria from the MalariaGEN dataset (<i>N</i> = 17,000) and lipid traits from summary-level data of a meta-analyzed African lipid GWAS (MALG, <i>N</i> = 24,215) from the African Partnership for Chronic Disease Research (APCDR) (<i>N</i> = 13,612) and the Africa Wits-IN-DEPTH partnership for genomics studies (AWI-Gen) dataset (<i>N</i> = 10,603).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 4","pages":"178-187"},"PeriodicalIF":1.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12555","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140130579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}