Background: The relationship between adiposity at birth and in childhood, and telomere length is yet to be determined. We aimed to systematically review and meta-analyse the results of studies ...assessing associations between neonatal and later childhood adiposity, and telomere length. Methods: We searched Medline, EMBASE and PubMed for studies reporting associations between adiposity measured in the neonatal period or later childhood/adolescence, and leucocyte telomere length, measured at any age via quantitative polymerase chain reaction, or terminal restriction fragment analysis, either cross-sectionally, or longitudinally. Papers published before April 2017 were included. Results: Out of 230 abstracts assessed, 23 papers (32 estimates) were retained, from which 19 estimates were meta-analysed (15 cross-sectional, four longitudinal). Of the 15 cross-sectional estimates, seven reported on neonates: four used binary exposures of small-for-gestational-age vs. appropriate-for-gestational age (or appropriate- and large-for-gestational age), and three studied birth weight continuously. Eight estimates reported on later childhood or adolescent measures; five estimates were from studies of binary exposures (overweight/obese vs. non-obese children), and three studies used continuous measures of body mass index. All four longitudinal estimates were of neonatal adiposity, with two estimates for small-for-gestational-age vs. appropriate-for-gestational age neonates, and two estimates of birth weight studied continuously, in relation to adult telomere (49-61 years). There was no strong evidence of an association between neonatal or later childhood/adolescent adiposity, and telomere length. However, between study heterogeneity was high, and there were few combinable studies. Conclusions: Our systematic review and meta-analysis found no strong evidence of an association between neonatal or later childhood or adolescent adiposity and telomere length.
: The relationship between adiposity at birth and in childhood, and telomere length is yet to be determined. We aimed to systematically review and meta-analyse the results of studies assessing ...associations between neonatal and childhood adiposity, and telomere length.
: We searched Medline, EMBASE and PubMed for studies reporting associations between adiposity measured in the neonatal period or childhood, and leucocyte telomere length, measured at any age via quantitative polymerase chain reaction, or terminal restriction fragment analysis, either cross-sectionally, or longitudinally. Papers published before April 2017 were included.
: Out of 230 abstracts assessed, 23 papers (32 estimates) were retained, from which 19 estimates were meta-analysed (15 cross-sectional, four longitudinal). Of the 15 cross-sectional estimates, seven reported on neonates: four used binary exposures of small-for-gestational-age vs. appropriate-for-gestational age (or appropriate- and large-for-gestational age), and three studied birth weight continuously. Eight estimates reported on childhood measures; five estimates were from studies of binary exposures (overweight/obese vs. non-obese children), and three studies used continuous measures of body mass index. All four longitudinal estimates were of neonatal adiposity, with two estimates for small-for-gestational-age vs. appropriate-for-gestational age neonates, and two estimates of birth weight studied continuously, in relation to adult telomere (49-61 years). There was no strong evidence of an association between neonatal or childhood adiposity, and telomere length. However, between study heterogeneity was high, and there were few combinable studies.
: Our systematic review and meta-analysis found no strong evidence of an association between neonatal or childhood adiposity and telomere length.
Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first ...genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females.
We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium.
Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10
) interactions with sex on lung function, and 21 showed suggestive interactions (P<1x10
). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV
) (P=3.15x10
), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV
more in males (untransformed FEV
β=0.028 SE 0.0022 litres) than females (β=0.009 SE 0.0014 litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein (
) gene and was previously associated with lung function and
lung expression. We found
expression was significantly different between the sexes (P=6.90x10
), but we could not detect sex differential effects of rs7697189 on expression.
We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the
gene. Establishing the mechanism by which
SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.
Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for ...SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types.
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•Identification of 23 genomic loci with suggestive associations for COVID-19 disease•Colocalized GWAS and eQTL signals associate with expression of 20 genes in 62 tissues•In total, 45% of GWAS signals do not colocalize with eQTLs in blood or lung•Genetic fine mapping identifies putative causal variants at COVID-19 GWAS loci
D’Antonio et al. characterize associations between GWAS signals for COVID-19 disease and eQTLs in 69 human tissues to identify causal variants and their underlying molecular mechanisms. They show that diverse symptoms and disease severity of COVID-19 are associated with variants affecting gene expression in a wide variety of tissues.
Background:
Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the ...first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females.
Methods:
We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium.
Results:
Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10
-8
) interactions with sex on lung function, and 21 showed suggestive interactions (P<1x10
-6
). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV
1
) (P=3.15x10
-15
), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV
1
more in males (untransformed FEV
1
β=0.028 SE 0.0022 litres) than females (β=0.009 SE 0.0014 litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein (
HHIP
) gene and was previously associated with lung function and
HHIP
lung expression. We found
HHIP
expression was significantly different between the sexes (P=6.90x10
-6
), but we could not detect sex differential effects of rs7697189 on expression.
Conclusions:
We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the
HHIP
gene. Establishing the mechanism by which
HHIP
SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.
There are limited data on the outcomes of COVID-19 risk assessment in healthcare workers (HCWs) or the association of ethnicity, other sociodemographic and occupational factors with risk assessment ...outcomes.
We used questionnaire data from UK-REACH (UK Research study into Ethnicity And COVID-19 outcomes in Healthcare workers), an ethnically diverse, nationwide cohort of UK HCWs. We derived four binary outcomes: (1) offered a risk assessment; (2) completed a risk assessment; (3) working practices changed as a result of the risk assessment; (4) wanted changes to working practices after risk assessment but working practices did not change.We examined the association of ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk variables on our outcomes using multivariable logistic regression.
8649 HCWs were included in total. HCWs from ethnic minority groups were more likely to report being offered a risk assessment than white HCWs, and those from Asian and black ethnic groups were more likely to report having completed an assessment if offered. Ethnic minority HCWs had lower odds of reporting having their work change as a result of risk assessment. Those from Asian and black ethnic groups were more likely to report no changes to their working practices despite wanting them.Previous SARS-CoV-2 infection was associated with lower odds of being offered a risk assessment and having adjustments made to working practices.
We found differences in risk assessment outcomes by ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk factors. These findings are concerning and warrant further research using actual (rather than reported) risk assessment outcomes in an unselected cohort.
Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 ...(SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs. We conducted a cross-sectional analysis using data from the baseline questionnaire of the United Kingdom Research study into Ethnicity and Coronavirus Disease 2019 (COVID-19) Outcomes in Healthcare workers (UK-REACH) cohort study, administered between December 2020 and March 2021. We used logistic regression to examine associations of demographic, household, and occupational risk factors with SARS-CoV-2 infection (defined by polymerase chain reaction (PCR), serology, or suspected COVID-19) in a diverse group of HCWs. The primary exposure of interest was self-reported ethnicity. We identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection among UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic.
Healthcare workers' (HCW) well-being has a direct effect on patient care. However, little is known about the prevalence and patterns of long-term medical conditions in HCWs, especially those from ...ethnic minorities. This study evaluated the burden of multiple long-term conditions (MLTCs), i.e. the presence of two or more single long-term conditions (LTCs), among HCWs in the United Kingdom (UK) and variation by ethnicity and migration status.
We used baseline data from the UK-REACH cohort study collected December 2020-March 2021. We used multivariable logistic regression, adjusting for demographic, occupational and lifestyle factors to examine the relationship between self-reported LTCs/MLTCs and ethnicity, migration status and time since migration to the UK.
Of 12,100 included HCWs, with a median age of 45 years (IQR: 34-54), 27% were overseas-born, and 30% were from non-White ethnic groups (19% Asian, 4% Black, 4% Mixed, 2% Other). The most common self-reported LTCs were anxiety (14.9%), asthma (12.2%), depression (10.7%), hypertension (8.7%) and diabetes (4.0%). Mental health conditions were more prevalent among UK-born than overseas-born HCWs for all ethnic groups (adjusted odds ratio (aOR) using White UK-born as the reference group each time: White overseas-born 0.77, 95%CI 0.66-0.95 for anxiety). Diabetes and hypertension were more common among Asian (e.g. Asian overseas, diabetes aOR 2.97, 95%CI 2.30-3.83) and Black (e.g. Black UK-born, hypertension aOR 1.77, 95%CI 1.05-2.99) groups than White UK-born. After adjustment for age, sex and deprivation, the odds of reporting MLTCs were lower in most ethnic minority groups and lowest for those born overseas, compared to White UK-born (e.g. White overseas-born, aOR 0.68, 95%CI 0.55-0.83; Asian overseas-born aOR 0.75, 95%CI 0.62-0.90; Black overseas-born aOR 0.52, 95%CI 0.36-0.74). The odds of MLTCs in overseas-born HCWs were equivalent to the UK-born population in those who had settled in the UK for ≥ 20 years (aOR 1.14, 95%CI 0.94-1.37).
Among UK HCWs, the prevalence of common LTCs and odds of reporting MLTCs varied by ethnicity and migrant status. The lower odds of MLTCs in migrant HCWs reverted to the odds of MLTCs in UK-born HCWs over time. Further research on this population should include longitudinal studies with linkage to healthcare records. Interventions should be co-developed with HCWs from different ethnic and migrant groups focussed upon patterns of conditions prevalent in specific HCW subgroups to reduce the overall burden of LTCs/MLTCs.
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