The Duffy-null genotype and risk of infection

Abstract Many medical treatments, from oncology to psychiatry, can lower white blood cell counts and thus access to these treatments can be restricted to individuals with normal levels of white blood cells, principally in order to minimize risk of serious infection. This adversely affects individuals of African or Middle Eastern ancestries who have on average a reduced number of circulating white blood cells, because of the Duffy-null (CC) genotype at rs2814778 in the ACKR1 gene. Here, we investigate whether the Duffy-null genotype is associated with the risk of infection using the UK Biobank sample and the iPSYCH Danish case-cohort study, two population-based samples from different countries and age ranges. We found that a high proportion of those with the Duffy-null genotype (21%) had a neutrophil count below the threshold often used as a cut-off for access to relevant treatments, compared with 1% of those with the TC/TT genotype. In addition we found that despite its strong association with lower average neutrophil counts, the Duffy-null genotype was not associated with an increased risk of infection, viral or bacterial. These results have widespread implications for the clinical treatment of individuals of African ancestry and indicate that neutrophil thresholds to access treatments could be lowered in individuals with the Duffy-null genotype without an increased risk of infection.

Download Full-text

Prioritizing Causal Risk Factors for Severe COVID-19: An Exhaustive Mendelian Randomization Study

10.21203/rs.3.rs-149087/v1 ◽

2021 ◽

Cited By ~ 1

Author(s):

Yitang Sun ◽

Jingqi Zhou ◽

Kaixiong Ye

Keyword(s):

Risk Factors ◽

Fat Mass ◽

Blood Cells ◽

Drug Targets ◽

Large Scale ◽

Mendelian Randomization ◽

White Blood Cells ◽

Fat Free Mass ◽

Cell Counts ◽

Increased Risk

Abstract Identifying causal risk factors for severe coronavirus disease 2019 (COVID-19) is critical for its prevention and treatment. Many associated pre-existing conditions and biomarkers have been reported, but these observational associations suffer from confounding and reverse causation. Here, we perform a large-scale two-sample Mendelian randomization (MR) analysis to evaluate the causal roles of many traits in severe COVID-19. Our results highlight multiple body mass index (BMI)-related traits as risk-increasing: BMI (OR:1.89, 95% CI:1.51–2.37), hip circumference (OR:1.46, 1.15–1.85), and waist circumference (OR:1.82, 1.36–2.43). Our multivariable MR analysis further shows that the BMI-related effect is driven by fat mass (OR:1.63, 1.03–2.58), but not fat-free mass (OR:1.00, 0.61–1.66). Several white blood cell counts are negatively associated with severe COVID-19, including those of neutrophils (OR:0.76, 0.61–0.94), granulocytes (OR:0.75, 0.601–0.93), and myeloid white blood cells (OR:0.77, 0.62–0.96). Furthermore, some circulating proteins are associated with an increased risk of (e.g., zinc-alpha-2-glycoprotein) or protection from severe COVID-19 (e.g., interleukin-3/6 receptor subunit alpha). Our study shows that fat mass and white blood cells underlie the etiology of severe COVID-19. It also identifies risk and protective factors that could serve as drug targets and guide the effective protection of high-risk individuals.

Download Full-text

Extensive Mendelian randomization study identifies potential causal risk factors for severe COVID-19

Communications Medicine ◽

10.1038/s43856-021-00061-9 ◽

2021 ◽

Vol 1 (1) ◽

Author(s):

Yitang Sun ◽

Jingqi Zhou ◽

Kaixiong Ye

Keyword(s):

Risk Factors ◽

Fat Mass ◽

Blood Cells ◽

Drug Targets ◽

Large Scale ◽

Mendelian Randomization ◽

White Blood Cells ◽

Fat Free Mass ◽

Cell Counts ◽

Increased Risk

Abstract Background Identifying causal risk factors for severe coronavirus disease 2019 (COVID-19) is critical for its prevention and treatment. Many associated pre-existing conditions and biomarkers have been reported, but these observational associations suffer from confounding and reverse causation. Methods Here, we perform a large-scale two-sample Mendelian randomization (MR) analysis to evaluate the causal roles of many traits in severe COVID-19. Results Our results highlight multiple body mass index (BMI)-related traits as risk-increasing: BMI (OR: 1.89, 95% CI: 1.51–2.37), hip circumference (OR: 1.46, 1.15–1.85), and waist circumference (OR: 1.82, 1.36–2.43). Our multivariable MR analysis further suggests that the BMI-related effect might be driven by fat mass (OR: 1.63, 1.03–2.58), but not fat-free mass (OR: 1.00, 0.61–1.66). Several white blood cell counts are negatively associated with severe COVID-19, including those of neutrophils (OR: 0.76, 0.61–0.94), granulocytes (OR: 0.75, 0.601–0.93), and myeloid white blood cells (OR: 0.77, 0.62–0.96). Furthermore, some circulating proteins are associated with an increased risk of (e.g., zinc-alpha-2-glycoprotein) or protection from severe COVID-19 (e.g., prostate-associated microseminoprotein). Conclusions Our study suggests that fat mass and white blood cells might be involved in the development of severe COVID-19. It also prioritizes potential risk and protective factors that might serve as drug targets and guide the effective protection of high-risk individuals.

Download Full-text

Migrant status and risk of compulsory admission at first diagnosis of psychotic disorder: a population-based cohort study in Sweden

Psychological Medicine ◽

10.1017/s0033291720002068 ◽

2020 ◽

pp. 1-10

Author(s):

J. Terhune ◽

J. Dykxhoorn ◽

E. Mackay ◽

A.-C. Hollander ◽

J. B. Kirkbride ◽

...

Keyword(s):

Psychotic Disorder ◽

Middle Eastern ◽

Population Based ◽

Compulsory Admission ◽

Migrant Status ◽

Region Of Origin ◽

Increased Risk ◽

National Register Data ◽

Sub Saharan ◽

First Diagnosis

Abstract Background Minority ethnic and migrant groups face an elevated risk of compulsory admission for mental illness. There are overlapping cultural, socio-demographic, and structural explanations for this risk that require further investigation. Methods By linking Swedish national register data, we established a cohort of persons first diagnosed with a psychotic disorder between 2001 and 2016. We used multilevel mixed-effects logistic modelling to investigate variation in compulsory admission at first diagnosis of psychosis across migrant and Swedish-born groups with individual and neighbourhood-level covariates. Results Our cohort included 12 000 individuals, with 1298 (10.8%) admitted compulsorily. In an unadjusted model, being a migrant [odds ratio (OR) 1.48; 95% confidence interval (CI) 1.26–1.73] or child of a migrant (OR 1.27; 95% CI 1.10–1.47) increased risk of compulsory admission. However after multivariable modelling, region-of-origin provided a better fit to the data than migrant status; excess risk of compulsory admission was elevated for individuals from sub-Saharan African (OR 1.94; 95% CI 1.51–2.49), Middle Eastern and North African (OR 1.46; 95% CI 1.17–1.81), non-Nordic European (OR 1.27; 95% CI 1.01–1.61), and mixed Swedish-Nordic backgrounds (OR 1.33; 95% CI 1.03–1.72). Risk of compulsory admission was greater in more densely populated neighbourhoods [OR per standard deviation (s.d.) increase in the exposure: 1.12, 95% CI 1.06–1.18], an effect that appeared to be driven by own-region migrant density (OR per s.d. increase in exposure: 1.12; 95% CI 1.02–1.24). Conclusions Inequalities in the risk of compulsory admission by migrant status, region-of-origin, urban living and own-region migrant density highlight discernible factors which raise barriers to equitable care and provide potential targets for intervention.

Download Full-text

ALLIUM SATIVUM ESSENTIAL OIL (ASEO);

The Professional Medical Journal ◽

10.29309/tpmj/2017.24.04.1519 ◽

2017 ◽

Vol 24 (04) ◽

pp. 612-616

Author(s):

Faisal Irshad ◽

Hina Mawani ◽

Sana Naz

Keyword(s):

Essential Oil ◽

Blood Cell ◽

Blood Cells ◽

Allium Sativum ◽

White Blood Cells ◽

Albino Rats ◽

Serum Triglycerides ◽

Cell Counts ◽

Blood Cell Counts ◽

Animal House

Objectives: To determine the effects of Allium sativum essential oil (ASEO)phytotherapy on serum triglycerides, total cholesterol, HDLc, LDLc and blood cell counts inalbino rat model. Study design: Experimental study. Setting and Duration: Animal House,Sindh Agriculture University and Isra University Hyderabad from May 2014 to January 2015.Materials and Methods: 60 albino rats were divided into four groups. Controls were givenPlacebo. Experimental rat groups were given ASEO 100 mg/kg, 200 mg/kg and 300 mg/kgorally for 30 days. Cardiac puncture was performed for blood sampling. Research variableswere analyzed on Statistix 10.0 (USA). Results: Blood lipids showed significant reduction invarious blood lipid fractions. Serum LDLc exhibited with a concomitant rise in serum HDLc (p=0.0001) in high ASEO treated rats. Red blood cells, white blood cells and platelet showedsignificant improvement ASEO fed rats (p=0.001). Conclusion: Allium sativum essential oil(ASEO) phytotherapy showed a rise in HDLc and a reduction in LDLc, triglycerides and totalcholesterol with improvement in red blood cell counts.

Download Full-text

Severity of COVID-19 in children with cancer: Report from the United Kingdom Paediatric Coronavirus Cancer Monitoring Project

British Journal of Cancer ◽

10.1038/s41416-020-01181-0 ◽

2020 ◽

Author(s):

Gerard C. Millen ◽

Roland Arnold ◽

Jean-Baptiste Cazier ◽

Helen Curley ◽

Richard G. Feltbower ◽

...

Keyword(s):

Severe Infection ◽

Paediatric Population ◽

Population Based ◽

Children With Cancer ◽

The United Kingdom ◽

Increased Risk ◽

Polymerase Chain ◽

The Uk ◽

Active Care ◽

Care Support

Abstract Background Children with cancer are frequently immunocompromised. While children are generally thought to be at less risk of severe SARS-CoV-2 infection than adults, comprehensive population-based evidence for the risk in children with cancer is unavailable. We aimed to produce evidence of the incidence and outcomes from SARS-CoV-2 in children with cancer attending all hospitals treating this population across the UK. Methods Retrospective and prospective observational study of all children in the UK under 16 diagnosed with cancer through data collection from all hospitals providing cancer care to this population. Eligible patients tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). The primary end-point was death, discharge or end of active care for COVID-19 for those remaining in hospital. Results Between 12 March 2020 and 31 July 2020, 54 cases were identified: 15 (28%) were asymptomatic, 34 (63%) had mild infections and 5 (10%) moderate, severe or critical infections. No patients died and only three patients required intensive care support due to COVID-19. Estimated incidence of hospital identified SARS-CoV-2 infection in children with cancer under 16 was 3%. Conclusions Children with cancer with SARS-CoV-2 infection do not appear at increased risk of severe infection compared to the general paediatric population. This is reassuring and supports the continued delivery of standard treatment.

Download Full-text

Genetically Determined Physical Activity and Its Association with Circulating Blood Cells

Genes ◽

10.3390/genes10110908 ◽

2019 ◽

Vol 10 (11) ◽

pp. 908 ◽

Cited By ~ 2

Author(s):

Femke M. Prins ◽

M. Abdullah Said ◽

Yordi J. van de Vegte ◽

Niek Verweij ◽

Hilde E. Groot ◽

...

Keyword(s):

Physical Activity ◽

Blood Cells ◽

Fixed Effects ◽

Mendelian Randomization ◽

P Value ◽

Nucleotide Polymorphisms ◽

Increased Risk ◽

Inflammatory State ◽

The Uk ◽

Genetically Determined

Lower levels of physical activity (PA) have been associated with increased risk of cardiovascular disease. Worldwide, there is a shift towards a lifestyle with less PA, posing a serious threat to public health. One of the suggested mechanisms behind the association between PA and disease development is through systemic inflammation, in which circulating blood cells play a pivotal role. In this study we investigated the relationship between genetically determined PA and circulating blood cells. We used 68 single nucleotide polymorphisms associated with objectively measured PA levels to perform a Mendelian randomization analysis on circulating blood cells in 222,645 participants of the UK Biobank. For inverse variance fixed effects Mendelian randomization analyses, p < 1.85 × 10−3 (Bonferroni-adjusted p-value of 0.05/27 tests) was considered statistically significant. Genetically determined increased PA was associated with decreased lymphocytes (β = –0.03, SE = 0.008, p = 1.35 × 10−3) and decreased eosinophils (β = –0.008, SE = 0.002, p = 1.36 × 10−3). Although further mechanistic studies are warranted, these findings suggest increased physical activity is associated with an improved inflammatory state with fewer lymphocytes and eosinophils.

Download Full-text

Arsenic, cadmium, and lead contents of rice imported into Qatar-impact on intake

British Food Journal ◽

10.1108/bfj-07-2019-0572 ◽

2019 ◽

Vol 122 (1) ◽

pp. 99-106 ◽

Cited By ~ 1

Author(s):

Tahra Elobeid ◽

Vijay Ganji ◽

Khloud Moustafa ◽

Fatima Mohammed ◽

Loujain El-Ouzi ◽

...

Keyword(s):

Heavy Metal ◽

Middle Eastern ◽

Population Based ◽

Arsenic Content ◽

Content Type ◽

The Usa ◽

Rice Consumption ◽

Rice Samples ◽

Cadmium And Lead ◽

The Uk

Purpose The purpose of this paper is to determine arsenic, cadmium and lead contents of rice imports and to estimate their impact on these heavy metal intakes in Qatar. Design/methodology/approach In total, 30 rice samples imported from various countries (Vietnam, Thailand, India, Pakistan, the USA, Australia, the UK and Lebanon) were analyzed for arsenic, cadmium and lead contents with plasma optical spectrometer. These heavy metal intakes from rice were estimated for Qatar population based on the per capita consumption of rice as per 2018 rice consumption data. Findings In all rice samples, mean concentrations of arsenic, cadmium and lead were 1.11 mg/kg, 19.7 µg/kg and 131.3 µg/kg, respectively. Average arsenic, cadmium and lead contents were the highest in rice imported from Thailand (1.25 mg/kg), Vietnam (30 µg/kg) and India (178.3 µg/kg), respectively. Estimated arsenic, cadmium and lead intakes through rice consumption by Qatari population were 225.7, 4 and 26.7 µg/day, respectively. Originality/value In all rice imports, arsenic content is approximately 5.5 times higher than the maximum allowable concentration (MAC), whereas the cadmium and lead levels are within the MAC. Because these heavy metals are linked to health, all Middle Eastern countries that import rice from Thailand, Vietnam and India should monitor the metal contents in their food supply on a regular basis.

Download Full-text

When Non-Whiteness Becomes a Condition

Blood ◽

10.1182/blood.2020008600 ◽

2020 ◽

Author(s):

Lauren E Merz ◽

Maureen Achebe

Keyword(s):

Predominantly White ◽

American Medical ◽

African Ancestry ◽

Medical System ◽

Risk Of Infection ◽

Systemic Racism ◽

European Descent ◽

White American ◽

Increased Risk ◽

Sub Saharan

The term "benign ethnic neutropenia" describes the phenotype of having an ANC less than 1500 cells/uL with no increased risk of infection. This is most commonly seen in those of African ancestry. In addition, ANC ranges from countries in Africa emphasize that ANC levels below 1500 cell/uL are common and harmless. The lower ANC levels are driven by the Duffy null [Fy(a-b-)] phenotype which is protective against malaria and seen in 80-100% of those of Sub-Saharan African ancestry and <1% of those of Caucasian descent. Benign ethnic neutropenia is clinically insignificant, but the average ANC values differ from what is typically seen in those of European descent. Thus, the predominantly white American medical system has described this as a condition. This labelling implicitly indicates that common phenotypes in non-white populations are abnormal or wrong. We feel that it is important to examine and rectify practices in hematology that contribute to systemic racism.

Download Full-text

Increased risk of all‐cause mortality associated with domperidone use in Parkinson's patients: a population‐based cohort study in the UK

British Journal of Clinical Pharmacology ◽

10.1111/bcp.13708 ◽

2018 ◽

Vol 84 (11) ◽

pp. 2551-2561 ◽

Cited By ~ 7

Author(s):

Marina Simeonova ◽

Frank Vries ◽

Sander Pouwels ◽

Johanna H. M. Driessen ◽

Hubert G.M. Leufkens ◽

...

Keyword(s):

Cohort Study ◽

Population Based ◽

Increased Risk ◽

All Cause Mortality ◽

The Uk

Download Full-text

Altered Cortical Brain Structure and Increased Risk for Disease Seen Decades After Perinatal Exposure to Maternal Smoking: A Study of 9000 Adults in the UK Biobank

Cerebral Cortex ◽

10.1093/cercor/bhz060 ◽

2019 ◽

Vol 29 (12) ◽

pp. 5217-5233 ◽

Cited By ~ 4

Author(s):

Lauren E Salminen ◽

Rand R Wilcox ◽

Alyssa H Zhu ◽

Brandalyn C Riedel ◽

Christopher R K Ching ◽

...

Keyword(s):

Brain Structure ◽

Brain Mri ◽

Population Based ◽

Smoke Exposure ◽

Sensitivity Analyses ◽

Uk Biobank ◽

Increased Risk ◽

Increase Risk ◽

Sensory Cortices ◽

The Uk

Abstract Secondhand smoke exposure is a major public health risk that is especially harmful to the developing brain, but it is unclear if early exposure affects brain structure during middle age and older adulthood. Here we analyzed brain MRI data from the UK Biobank in a population-based sample of individuals (ages 44–80) who were exposed (n = 2510) or unexposed (n = 6079) to smoking around birth. We used robust statistical models, including quantile regressions, to test the effect of perinatal smoke exposure (PSE) on cortical surface area (SA), thickness, and subcortical volumes. We hypothesized that PSE would be associated with cortical disruption in primary sensory areas compared to unexposed (PSE−) adults. After adjusting for multiple comparisons, SA was significantly lower in the pericalcarine (PCAL), inferior parietal (IPL), and regions of the temporal and frontal cortex of PSE+ adults; these abnormalities were associated with increased risk for several diseases, including circulatory and endocrine conditions. Sensitivity analyses conducted in a hold-out group of healthy participants (exposed, n = 109, unexposed, n = 315) replicated the effect of PSE on SA in the PCAL and IPL. Collectively our results show a negative, long term effect of PSE on sensory cortices that may increase risk for disease later in life.

Download Full-text