Sunday, May 24, 2020

Allelic variants found only in populations of African ancestry predict kidney disease and preeclampsia in blacks

Black women in the United States and Africa are at an increased risk for preeclampsia. Allelic variants in the gene for apolipoprotein LI, APOL1, are found only in populations of African ancestry, and have been shown to contribute significant risk for kidney disease. Recent studies suggest these APOL1 variants also may contribute risk for preeclampsia.

Methods

The association of preeclampsia with carriage of APOL1 risk alleles was evaluated in a case-control study of deliveries from black women at a single center in Cleveland, Ohio that included gross and histopathologic evaluations of placental tissues (395 cases and 282 controls). Using logistic regression models, associations between fetal APOL1 genotype and preeclampsia were evaluated using several case definitions based on prematurity and severity of preeclampsia, with uncomplicated term pregnancies as controls. Associations between APOL1 genotype and pathological features were also examined.

Results

The infant APOL1 genotype was significantly associated with preeclampsia in a dominant inheritance pattern with odds ratio of 1.41 (P=0.029, 95% CI 1.037, 1.926). Stratifying preeclampsia cases by preterm birth, significant associations were detected for both recessive (O.R.=1.70, P=0.038) and additive (O.R.=1.33, P=0.028) inheritance patterns.

Thursday, May 14, 2020

Genetic risk scores for obesity based on European populations work for Roma, too

Abstract from the journal Genes:

Investigations on the impact of genetic factors on the development of obesity have been limited regarding the Roma population—the largest and most vulnerable ethnic minority in Europe of Asian origin. Genetic variants identified from genetic association studies are primarily from European populations.

With that in mind, we investigated the applicability of data on selected obesity‐related single nucleotide polymorphisms (SNPs), obtained from the Hungarian general (HG) population of European origin, on the Hungarian Roma (HR) population.

Twenty preselected SNPs in susceptible alleles, known to be significantly associated with obesity‐related phenotypes, were used to estimate the effect of these SNPs on body mass index (BMI) and waist circumference (WC) in HG (N = 1783) and HR (N = 1225) populations. Single SNP associations were tested using linear and logistic regression models, adjusted for known covariates.

Out of 20 SNPs, four located in FTO (rs1121980, rs1558902, rs9939609, and rs9941349) showed strong association with BMI and WC as continuous variables in both samples. Computations based on Adult Treatment Panel III (ATPIII) and the International Diabetes Federation’s (IDF) European and Asian criteria showed rs9941349 in FTO to be associated only with WC among both populations, and two SNPs (rs2867125, rs6548238) in TMEM18 associated with WC only in HG population. A substantial difference (both in direction and effect size) was observed only in the case of rs1801282 in PPAR╬│ on WC as a continuous outcome.

Findings suggest that genetic risk scores based on counting SNPs with relatively high effect sizes, defined based on populations with European ancestry, can sufficiently allow estimation of genetic susceptibility for Roma. Further studies are needed to clarify the role of SNP(s) with protective effect(s).

Wednesday, May 13, 2020

BMJ Editorial: Is ethnicity linked to incidence or outcomes of covid-19?

Dear Editor
COVID-19 (Coronavirus) mortality disproportionately impacts BAME (Black, Asian and Minority Ethnic) UK individuals, African Americans, Swedish Somalis,[1] and the institutionalised; particularly care-home residents. COVID-19 severity and mortality, appear related to vitamin D deficiency, [2 -12] helping explain higher COVID-19 mortality rates in BAME and the obese.[13]

Obesity is a strong COVID-19 risk factor, as are co-morbidities, including diabetes, cardio-vascular disease; and sedentary lifestyle; all are dependent on mitochondrial functionality (Gnaiger).[14] Fat cells accrete vitamin D.[15] The obese consistently have proportionately lower vitamin D status (serum 25-hydroxyvitamin D [25(OH)D]).[16]

Vitamin D is a secosteroid hormone with various skeletal and non-skeletal effects including regulation of innate and adaptive immune responses. Vitamin D, by binding to the vitamin D response element in various gene-promoter-regions, decreases expression of pro-inflammatory-cytokines and increases production of antiviral and antibacterial[17] proteins, suggesting an important role in antiviral innate adaptive immunity.[18] Importantly, vitamin D is also involved in renin–angiotensin system regulation,[19] which is regulated by entry of the SARS-Cov-2 virus into cells via the ACE2 receptor, leading to cytokine storms, with subsequent fatal respiratory distress syndrome.[20]...

Currently, no effective COVID-19 treatment exists. Vaccines present enormous possibilities, but equally-large hurdles, and require time. Vitamin D biology, is a mature well-researched field, dating back 100 years. Doses, and risks, within clinical parameters, are established and well quantified. Governmental intake guidance exists. Vitamin D deficiency is a medically accepted condition, requiring treatment. Existing blood samples from COVID-19 hospitalized patients could be retrospectively tested for 25(OH)D and linked to outcomes.[25]

We and others (Grant, Lahore)[9, 34] hypothesize vitamin D may have clinical COVID-19 relevance. Vitamin D deficiency may biomark risk of sepsis in all populations; 25(OH)D was significantly lower in patients that died within 30 days.[35, 36] A French clinical RCT recently started, testing effects of a large single vitamin D dose, administered early in infection, compared to a standard dose, on the mortality of older COVID-19 infected adults deficient in vitamin D (Annweiler).[37]

Whilst clinical studies have potential, vitamin D deficiency is an existing, ubiquitous and pressing issue. Deficiency is variable, but widespread globally. BAME people in high latitudes are a group at high risk of deficiency, as observed by NICE[38] and others (Rhein).[39] Surprisingly, vitamin D may be a larger relative COVID-19 causative agent than socioeconomic-factors.[40] Importantly, vitamin D supplementation determinants should include basal level, genetic background, metabolic status and gender.

Albeit vitamin D deficiency most likely accounts for a greater COVID-19 impact on BAME, older, institutionalised and obese persons, COVID-19 severity would undoubtedly be exacerbated by, often socioeconomic related, general micro-nutrient inadequacies.[41, 42]...

Recognition (subject to proof by research), that vitamin D deficiency contributes to COVID-19 infection, progression, severity and mortality would demand policy rethinking on: the seasonality of COVID-19,[43] outdoor access, motivation for physical exercise, food fortification, supplementation, clinical treatment, and provision of free vitamin D supplements to institutions, front-line health and care workers. Sensible (according to latitude and weather) sun exposure is free, available to all and quickly improves vitamin D status, but is inhibited by lock-down...

Friday, May 08, 2020

New study: More African ancestry predicts reduced lung function in Puerto Ricans


















Abstract

Introduction: In the U.S., asthma disproportionately affects urban minority populations, with Puerto Ricans showing the highest asthma prevalence 16.1%. However, what causes high asthma
prevalence among the Puerto Ricans is not very well understood. The varying proportions of African, European, and Native American genetic ancestry in Puerto Ricans can be leveraged to identify genetic determinants of clinically significant measures and outcomes such as lung function and asthma severity. We have previously demonstrated that genetic ancestry is associated with lung function.

Methods: In this current study, we sought to discover potential causal genes that may be associated with lung function in Puerto Rican islanders by applying admixture and fine mapping methods. A genome-wide admixture mapping study of lung function was conducted in 841 Puerto Rican children with and without asthma, who were recruited from Puerto Rico. After mapping admixture segments, we fine-mapped the genomic region using whole genome sequencing data. RNA-seq and eQTL mapping were used to elucidate underlying biologic links between genetic variants and lung function.

Results: The association test between local genetic ancestry and forced expiratory volume in 1 second (FEV1) identified a strong admixture mapping peak on chromosome 1q32, indicating that each African ancestry allele was associated with a 0.13 liter decrease in the volume of exhaled air [95%CI: -0.08 to -0.18, p-value=4.90×10-8]. Three variants identified from the fine-mapping analysis were eQTL of TMEM9 gene in nasal epithelial cell. The minor allele of the variant associated with TMEM9 gene (rs10920079) tracked with African ancestry and was associated with significantly decreased lung function and TMEM9 gene expression. TMEM9 was inversely correlated with proinflammatory cytokine IL-6 and IL-1╬▓ gene expressions.

Conclusion: The results from admixture mapping discovered variants that were associated with decreased lung function. Functional annotation and validation with RNA-seq and eQTL mapping indicate that these SNPs may be involved with regulating cytokine production, which may influence the lung function of Puerto Ricans.

Tuesday, May 05, 2020

Study: More Amerindian ancestry confers significant protection against onset of Alzheimer's


Abstract
Background: Alzheimer’s disease (AD) is the most common form of dementia worldwide, and bears remarkable evidence for a differential prevalence among continental populations. In this scenario, estimating ancestry proportions in recently admixed populations is a strategy that can help increasing knowledge about the genetic structure of this complex trait.

Aim/Methods: Our purpose was to assess mean ancestry estimates for the three main parental contributors to the Brazilian contingent (European, African and Amerindian) using a panel of 12 ancestry informative markers. Outpatients with the late-onset form of AD (n = 120) were compared for ancestry levels with non-cognitively impaired subjects (n = 412) in the Midwest Brazil, controlling for classic clinical, social and anthropometric risk factors.

Results: Our findings show a 3-fold greater genetic Amerindian content among control subjects compared to AD patients (p < 0.001).

Conclusion: Our results suggest that the allelic architecture of Native Americans can confer protection against the onset of the disease.


See how anti-Native American racism destroys... oh, I guess it doesn't work this time.

Study: Prostate cancer associated with more African ancestry among Brazilians

From Genetics and Molecular Research:

"We genotyped 11 ancestry informative markers to estimate the contributions of African, European, and Amerindian ancestries in a case-control sample of 213 individuals from Bahia State, Northeast Brazil, including 104 prostate cancer patients. We compared this data with self-reported ancestry and the stratification of cases by prostate cancer aggressiveness according to Gleason score. A larger African genetic contribution (44%) was detected among cases, and a greater European
contribution (61%) among controls."

But don't forget: Race has nothing to do with genes.


Study of 94k Americans: Irreligious blacks do much more drug selling and theft than religious blacks

This study , using a sample of ~94k teens and young adults, examined the link between religiosity (church attendance and saying religion is ...