325 results found
Muilwijk M, Loh M, Mahmood S, et al., 2022, The iHealth-T2D study: a cluster randomised trial for the prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes-a statistical analysis plan, TRIALS, Vol: 23
Dixon PH, Levine AP, Cebola I, et al., 2022, GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements, Nature Communications, Vol: 13, ISSN: 2041-1723
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1,138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility.
Leong W-Y, Gupta A, Hasan M, et al., 2022, Reference equations for evaluation of spirometry function tests in South Asia, and amongst South Asians living in other countries, European Respiratory Journal, ISSN: 0903-1936
Background:There is little data to accurate interpretation of spirometry data in SouthAsia, a major global region with high reported burden for chronicrespiratory disease.Method:We measured lung function in 7,453 healthy men and women aged over18 years, from Bangladesh, North India, South India, Pakistan and SriLanka, as part of the South Asia Biobank study. We first assessed theaccuracy of existing equations for predicting normal forced vital capacity(FVC), forced expiratory volume in 1s (FEV1), and FEV1/FVC ratio. Wethen used our data to derive (N=5,589) and internally validate(N=1,864) new prediction equations amongst South Asians, with furtherexternal validation amongst 339 healthy South Asians living inSingapore.Results:GLI2012 and NHANESIII consistently overestimated expiratory volumes(best fit GLI-SEA, mean [sd] z-score: FEV1 -1.29 [1.04]; FVC -1.12[1.12]). Age, height and weight were strong predictors of lung functionin our participants (P<0.001), and sex specific reference equations usingthese three variables were highly accurate in both internal validation (z-scores: FEV1 0.03 [0.99]; FVC 0.04 [0.97]; FEV1/FVC -0.03 [0.99]) andexternal validation (z-scores: FEV1 0.31 [0.99]; FVC 0.24 [0.97];FEV1/FVC 0.16 [0.91]). Further adjustment for study regions improvesthe model fit, with highest accuracy for estimation of region specific lungfunction in South Asia.Conclusion:We present improved equations for predicting lung function in SouthAsians. These offer the opportunity to enhance diagnosis andmanagement of acute and chronic lung diseases in this major globalpopulation.
Mahajan A, Spracklen CN, Zhang W, et al., 2022, Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation, NATURE GENETICS, Vol: 54, Pages: 560-+, ISSN: 1061-4036
Loh M, Zhang W, Ng HK, et al., 2022, Identification of genetic effects underlying type 2 diabetes in South Asian and European populations (vol 5, 329, 2022), COMMUNICATIONS BIOLOGY, Vol: 5
Jarvelin M-R, 2022, DNA methylation signature of chronic low-gradeinflammation and its role in cardio-respiratorydiseases, Nature Communications, Vol: 13, ISSN: 2041-1723
We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.
Loh M, Zhang W, Ng HK, et al., 2022, Identification of genetic effects underlying Type 2 Diabetes in South Asian and European populations, Communications Biology, Vol: 5, ISSN: 2399-3642
South Asians are at high risk of developing type 2 diabetes (T2D). We carried out a genome-wide association meta-analysis with South Asian T2D cases (n=16,677) and controls (n=33,856), followed by combined analyses with Europeans (neff=231,420). We identify 21 novel genetic loci for significant association with T2D (P=4.7x10-8 to 5.2x10-12), to the best of our knowledge at the point of analysis. The loci are enriched for regulatory features, including DNA methylation and gene expression in relevant tissues, and highlight CHMP4B, PDHB, LRIG1 and other genes linked to adiposity and glucose metabolism. A polygenic risk score based on South Asian-derived summary statistics shows ~4-fold higher risk for T2D between the top and bottom quartile. Our results provide further insights into the genetic mechanisms underlying T2D, and highlight the opportunities for discovery from joint analysis of data from across ancestral populations.
Ruamviboonsuk P, Tiwari R, Sayres R, et al., 2022, Real-time diabetic retinopathy screening by deep learning in a multisite national screening programme: a prospective interventional cohort study, LANCET DIGITAL HEALTH, Vol: 4
Warren H, Edwards T, Vaez A, et al., 2022, Genome-wide analysis in over 1 million individuals reveals over 2,000 independent genetic signals for blood pressure
<jats:title>Abstract</jats:title> <jats:p>Hypertension is a leading cause of premature death affecting more than a billion individuals worldwide. Here we report on the genetic determinants of blood pressure (BP) traits (systolic, diastolic, and pulse pressure) in the largest single-stage genome-wide analysis to date (N = 1,028,980 European-descent individuals). We identified 2,103 independent genetic signals (P < 5x10<jats:sup>− 8</jats:sup>) for BP traits, including 113 novel loci. These associations explain ~ 40% of common SNP heritability of systolic and diastolic BP. Comparison of top versus bottom deciles of polygenic risk scores (PRS) based on these results reveal clinically meaningful differences in BP (12.9 mm Hg for systolic BP, 95% CI 11.5–14.2 mm Hg, p = 9.08×10<jats:sup>− 73</jats:sup>) and hypertension risk (OR 5.41; 95% CI 4.12 to 7.10; P = 9.71×10<jats:sup>− 33</jats:sup>) in an independent dataset. Compared with the area under the curve (AUC) for hypertension discrimination for a model with sex, age, BMI, and genetic ancestry, adding systolic and diastolic BP PRS increased discrimination from 0.791 (95% CI = 0.781–0.801) to 0.814 (95% CI = 0.805–0.824, ∆AUC = 0.023, P = 2.27x10<jats:sup>− 22</jats:sup>). Our transcriptome-wide association study detected 2,793 BP colocalized associations with genetically-predicted expression of 1,070 genes in five cardiovascular tissues, of which 500 are previously unreported for BP traits. These findings represent an advance in our understanding of hypertension and highlight the role of increasingly large genomic studies for development of more accurate PRS, which may inform precision health research.</jats:p>
Fraszczyk E, Spijkerman AMW, Zhang Y, et al., 2022, Epigenome-wide association study of incident type 2 diabetes: a meta-analysis of five prospective European cohorts, DIABETOLOGIA, Vol: 65, Pages: 763-776, ISSN: 0012-186X
Hawe JS, Wilson R, Schmid KT, et al., 2022, Genetic variation influencing DNA methylation provides insights into molecular mechanisms regulating genomic function, NATURE GENETICS, Vol: 54, Pages: 18-+, ISSN: 1061-4036
Seneviratne S, Desloge A, Haregu T, et al., 2022, Characteristics and Outcomes of Community Health Worker Training to Improve the Prevention and Control of Cardiometabolic Diseases in Low and Middle-Income Countries: A Systematic Review., Inquiry, Vol: 59
Community health workers (CHWs) play an important role in controlling non-communicable diseases in low- and middle-income countries. The aim of this review was to describe the characteristics and outcomes of CHW training programs that focused on the prevention and control of cardiometabolic diseases in low- and middle-income countries (LMICs). Medline, CINAHL Complete, Academic Search Complete, Directory of Open Access Journal, ScienceDirect, ERIC, Gale Academic, and OneFile). Studies that described the training programs used to train CHWs for prevention and control of cardiovascular diseases and type2 diabetes mellitus in LMICs. Only studies that evaluated the outcomes of training programs in at least one of the 4 levels of Kirkpatrick's training evaluation model were included in the review. CHWs who underwent training focused on the prevention and control of cardiovascular disease and type 2 diabetes mellitus. We summarized the resulting evidence using qualitative synthesis through a narrative review. Training outcomes were assessed in relation to (1) CHW reactions to training, their degree of learning, and their behaviors following training, and (2) changes in biochemical and anthropometric indicators in target populations following the CHW program implementation. PROSPERO (CRD42020162116). Thirty-two studies were included. Methods used to train CHWs included: face-to-face lectures, interactive group activities, and blended teaching with online support. Training focused on identifying people with elevated risk of cardiometabolic diseases and their risk factors as well as supporting people to adopt healthy lifestyles. Many studies that utilized trained CHWs did not publish CHW training methods and evaluations, and therefore could not be included in this study. Training programs resulted in an increase in knowledge and skills among CHWs demonstrating that there are certain activities that can be shifted to CHWs following training.
Kasturiratne A, Khawaja KI, Ahmad S, et al., 2021, The iHealth-T2D study, prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes: study protocol for a randomised controlled trial, TRIALS, Vol: 22
Schlosser P, Tin A, Matias-Garcia PR, et al., 2021, Meta-analyses identify DNA methylation associated with kidney function and damage, NATURE COMMUNICATIONS, Vol: 12
Graham SE, Clarke SL, Wu K-HH, et al., 2021, The power of genetic diversity in genome-wide association studies of lipids, NATURE, Vol: 600, Pages: 675-+, ISSN: 0028-0836
Chen Y, Kassam I, Lau SH, et al., 2021, Impact of BMI and waist circumference on epigenome-wide DNA methylation and identification of epigenetic biomarkers in blood: an EWAS in multi-ethnic Asian individuals, CLINICAL EPIGENETICS, Vol: 13, ISSN: 1868-7075
Muilwijk M, Loh M, Siddiqui S, et al., 2021, Effects of a lifestyle intervention programme after 1 year of follow-up among South Asians at high risk of type 2 diabetes: a cluster randomised controlled trial, BMJ GLOBAL HEALTH, Vol: 6, ISSN: 2059-7908
Goyal S, Tanigawa Y, Zhang W, et al., 2021, APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups, LIPIDS IN HEALTH AND DISEASE, Vol: 20
Ranjani H, Nitika S, Hariharan R, et al., 2021, Systematic review and scientific rating of commercial apps available in India for diabetes prevention, JOURNAL OF DIABETOLOGY, Vol: 12, Pages: 285-+, ISSN: 2543-3288
Song P, Gupta A, Goon IY, et al., 2021, Data resource profile: Understanding the patterns and determinants of health in South Asians—the South Asia Biobank, International Journal of Epidemiology, Vol: 50, Pages: 717-718e, ISSN: 0300-5771
Goodrich JK, Singer-Berk M, Son R, et al., 2021, Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes, NATURE COMMUNICATIONS, Vol: 12, ISSN: 2041-1723
Chen J, Spracklen CN, Marenne G, et al., 2021, The trans-ancestral genomic architecture of glycemic traits, Nature Genetics, Vol: 53, Pages: 840-860, ISSN: 1061-4036
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
Surendran P, Feofanova EV, Lahrouchi N, et al., 2021, Publisher Correction: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals, Nature Genetics, Vol: 53, Pages: 1-2, ISSN: 1061-4036
Kusuma D, Pradeepa R, Khawaja KI, et al., 2021, Low uptake of COVID-19 prevention behaviours and high socioeconomic impact of lockdown measures in South Asia: evidence from a large-scale multi-country surveillance programme, SSM - Population Health, Vol: 13, ISSN: 2352-8273
Background. South Asia has become a major epicentre of the COVID-19 pandemic. Understanding South Asians’ awareness, attitudes and experiences of early measures for the prevention of COVID-19 is key to improving the effectiveness and mitigating the social and economic impacts of pandemic responses at a critical time for the Region. Methods. We assessed the knowledge, behaviours, health and socio-economic circumstances of 29,809 adult men and women, at 93 locations across four South Asian countries. Data were collected during the national lockdowns implemented from March to July 2020, and compared with data collected prior to the pandemic as part of an ongoing prospective surveillance initiative. Results. Participants were 61% female, mean age 45.1 years. Almost half had one or more chronic disease, including diabetes (16%), hypertension (23%) or obesity (16%). Knowledge of the primary COVID-19 symptoms and transmission routes was high, but access to hygiene and personal protection resources was low (running water 63%, hand sanitisers 53%, paper tissues 48%). Key preventive measures were not widely adopted. Knowledge, access to, and uptake of COVID-19 prevention measures were low amongst people from disadvantaged socio-economic groups. Fifteen percent of people receiving treatment for chronic diseases reported loss of access to long-term medications; 40% reported symptoms suggestive of anxiety or depression. The prevalence of unemployment rose from 9.3% to 39.4% (P<0.001), and household income fell by 52% (P<0.001) during the lockdown. Younger people and those from less affluent socio-economic groups were most severely impacted. Sedentary time increased by 32% and inadequate fruit and vegetable intake increased by 10% (P<0.001 for both), while tobacco and alcohol consumption dropped by 41% and 80%, respectively (P<0.001), during the lockdown.Conclusions. Our results identified important knowledge, access and uptake barriers to the prevention of COV
Karczewski KJ, Francioli LC, Tiao G, et al., 2021, Author Correction: The mutational constraint spectrum quantified from variation in 141,456 humans, Nature, Vol: 590, Pages: E53-E53, ISSN: 0028-0836
Minikel EV, Karczewski KJ, Martin HC, et al., 2021, Evaluating drug targets through human loss-of-function genetic variation (vol 581, pg 459, 2020), Nature, Vol: 590, Pages: E56-E56, ISSN: 0028-0836
Whiffin N, Karczewski KJ, Zhang X, et al., 2021, Characterising the loss-of-function impact of 5 ' untranslated region variants in 15,708 individuals (vol 11, 2523, 2020), Nature Communications, Vol: 12, Pages: 1-1, ISSN: 2041-1723
Wang Q, Pierce-Hoffman E, Cummings BB, et al., 2021, Author Correction: Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes., Nature Communications, Vol: 12, Pages: 1-1, ISSN: 2041-1723
Cummings BB, Karczewski KJ, Kosmicki JA, et al., 2021, Author Correction: Transcript expression-aware annotation improves rare variant interpretation.
Collins RL, Brand H, Karczewski KJ, et al., 2021, Author Correction: A structural variation reference for medical and population genetics.
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