Integrating Linguistics, Social Structure, and Geography to Model Genetic Diversity within India

Bose, Aritra; Platt, Daniel E.; Parida, Laxmi; Drineas, Petros; Paschou, Peristera

doi:10.1093/molbev/msaa321

Cited by 10 publications

(7 citation statements)

References 60 publications

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“…In the UK Biobank, people of south Asian origin had a lower frequency of genetic variants predisposing to subcutaneous adiposity compared with the white population, which might predispose them to increased visceral adiposity and adipocyte hypertrophy, resulting in β-cell glucolipotoxicity 67 . Because the population of India is particularly genetically complex owing to endogamy and diverse sociolinguistic groupings 68 , large sample sizes are required to ensure adequately powered GWAS and to stratify by Indian subpopulation 69 .…”

Section: Pathophysiological Mechanismsmentioning

confidence: 99%

Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations

et al. 2022

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| Nearly half of all adults with type 2 diabetes mellitus (T2DM) live in India and China. These populations have an underlying predisposition to deficient insulin secretion, which has a key role in the pathogenesis of T2DM. Indian and Chinese people might be more susceptible to hepatic or skeletal muscle insulin resistance, respectively, than other populations, resulting in specific forms of insulin deficiency. Cluster-based phenotypic analyses demonstrate a higher frequency of severe insulin-deficient diabetes mellitus and younger ages at diagnosis, lower β-cell function, lower insulin resistance and lower BMI among Indian and Chinese people compared with European people. Individuals diagnosed earliest in life have the most aggressive course of disease and the highest risk of complications. These characteristics might contribute to distinctive responses to glucose-lowering medications. Incretin-based agents are particularly effective for lowering glucose levels in these populations; they enhance incretin-augmented insulin secretion and suppress glucagon secretion. Sodium-glucose cotransporter 2 inhibitors might also lower blood levels of glucose especially effectively among Asian people, while α-glucosidase inhibitors are better tolerated in east Asian populations versus other populations. Further research is needed to better characterize and address the pathophysiology and phenotypes of T2DM in Indian and Chinese populations, and to further develop individualized treatment strategies.

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Section: Pathophysiological Mechanismsmentioning

confidence: 99%

Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations

et al. 2022

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“…It is worth noting that there is a long line of research on matrix sketching methods, including gaussian sketching, the use of the subsampled randomized hadamard transforms, the count-min sketch, etc. and its application in human genetics [1][2][3]. In our work, we evaluated both the count-min sketch and the gaussian sketch.…”

Section: Mask-lmmmentioning

confidence: 99%

MaSk-LMM: A Matrix Sketching Framework for Linear Mixed Models in Association Studies

Burch,

Bose,

Dexter

et al. 2023

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Linear mixed models (LMMs) have been widely used in genome-wide association studies (GWAS) to control for population stratification and cryptic relatedness. Unfortunately, estimating LMM parameters is computationally expensive, necessitating large-scale matrix operations to build the genetic relatedness matrix (GRM). Over the past 25 years, Randomized Linear Algebra has provided alternative approaches to such matrix operations by leveragingmatrix sketching, which often results in provably accurate fast and efficient approximations. We leveragematrix sketchingto develop a fast and efficient LMM method calledMatrix-SketchingLMM(MaSk-LMM) by sketching the genotype matrix to reduce its dimensions and speed up computations. Our framework comes with both theoretical guarantees and a strong empirical performance compared to current state-of-the-art.

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“…India has a unique advantage of genetic diversity, which is reasonably ascertained by their native language. The country also boasts of contrasting geographical and environmental factors, a combined view of which enables us to determine the genetic background of individuals [ 12 ]. We intend to use this diversity to establish the association of vitamin D levels with clinical phenotype in lupus.…”

Section: Introductionmentioning

confidence: 99%

Clinical and serological association of plasma 25-hydroxyvitamin D (25(OH)D) levels in lupus and the short-term effects of oral vitamin D supplementation

et al. 2023

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Background and objectives Data on the association of vitamin D levels and clinical phenotype and disease activity in systemic lupus erythematosus (SLE) is controversial. Further, the optimal dose of oral vitamin D supplementation in SLE is not clear. Thus, the present study was designed to determine the association of plasma vitamin D levels with clinical phenotype, disease variables and serology in a large, cohort of SLE from South Asia and to evaluate the short-term effect of two different dosage regimens of oral vitamin D supplementation on disease flares and plasma vitamin D levels. Methods This is a two-phase study. Phase I was a cross-sectional analytical study of patients from north (26.85° N) and south India (11.94° N). Plasma 25-hydroxyvitamin-D(25(OH)D) was measured, and its association with demography, serology, disease activity, Galectin-9 and CXCL-10 was analysed. In phase II, patients with SLEDAI-2KG < 10 and on stable immunosuppression were randomised to receive either high dose (weekly 60,000 U*5, followed by 60,000 U monthly) or routine dose (30,000 U monthly) oral vitamin D. Outcomes were assessed at 6 months Results Phase I included 702 patients with a mean age of 29.46 + 10.7 years. The median plasma vitamin D was 22.83 (13.8–31.8) ng/ml. Deficiency (< 20 ng/ml) was seen in 41.5% of patients. Patients from South India had higher vitamin D levels (27.06 ± 20.21 ng/dl) as compared to North India (17.15 ± 16.07 ng/ml) (p < 0.01). Univariate analyses demonstrated weak negative correlation of vitamin D with SLEDAI2K and positive correlation with age. Galactin-9 had modest correlation with SLEDAI2K but not with vitamin D levels. On multiple linear regression, centre of recruitment (β = 4.37) and age (β = 0.18) predicted (p < 0.05) plasma vitamin D levels. In the phase II, 91 randomised to 2 groups completed 6 months. Median change in plasma vitamin D levels was more in high dose (9.5 versus 2.6 ng/ml; p = 0.04). There were 14 SLE flares and six minor adverse events which were equal across both groups. Conclusion Vitamin D deficiency is common in SLE. Geographical location of residence is the major determinant rather than the disease activity. The IFN regulated proteins reflect disease activity independent of vitamin D levels. High-dose oral vitamin D supplementation seems safe and more effective in improving vitamin D levels in SLE. Trial registration The second phase of this study was a registered randomised controlled trial CTRI/2019/06/019658 [registered on: 14/06/2019].

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Integrating Linguistics, Social Structure, and Geography to Model Genetic Diversity within India

Cited by 10 publications

References 60 publications

Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations

Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations

MaSk-LMM: A Matrix Sketching Framework for Linear Mixed Models in Association Studies

Clinical and serological association of plasma 25-hydroxyvitamin D (25(OH)D) levels in lupus and the short-term effects of oral vitamin D supplementation

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