IndiGenomes: a comprehensive resource of genetic variants from over 1000 Indian genomes.

With the advent of next-generation sequencing, large-scale initiatives for mining whole genomes and exomes have been employed to better understand global or population-level genetic architecture. India encompasses more than 17% of the world population with extensive genetic diversity, but is under-represented in the global sequencing datasets. This gave us the impetus to perform and analyze the whole genome sequencing of 1029 healthy Indian individuals under the pilot phase of the 'IndiGen' program. We generated a compendium of 55,898,122 single allelic genetic variants from geographically distinct Indian genomes and calculated the allele frequency, allele count, allele number, along with the number of heterozygous or homozygous individuals. In the present study, these variants were systematically annotated using publicly available population databases and can be accessed through a browsable online database named as 'IndiGenomes' http://clingen.igib.res.in/indigen/. The IndiGenomes database will help clinicians and researchers in exploring the genetic component underlying medical conditions. Till date, this is the most comprehensive genetic variant resource for the Indian population and is made freely available for academic utility. The resource has also been accessed extensively by the worldwide community since it's launch.

Methodology for the early identification of neurodevelopmental disorders in the primary and preschool children in rural India by applying intervention module developed for teachers.

Objective: Neurodevelopmental disorders NDD are neurologic processing problems that interfere with learning in children. Primary and preschool teachers who are essential links in public health reach out to such children do not receive any formal training to identify these disorders. Hence, a primary and preschool level intervention addressing the issue is proposed. Materials and Methods: Primary and preschool teachers of government and government-aided schools and Anganwadi/preschools in the Model Rural Health Research Unit Tirunelveli field practice area will be assigned into two groups. The training module will be developed and validated using neurodevelopmental screening tool (NDST). Before identifying the students using the NDST, the teachers in Group A will get training using the module. Group B is the control group, in which untrained teachers administer the NDST to the children and then will be trained. Neurologists will assess the same children over 1 year. Results: The effectiveness of teacher training for the early detection of children with NDD will be assessed. Thus, the validity of the screening for NDD by the teachers will be estimated. Conclusion: If successful, the module can be incorporated into the Rashtriya Bal Swasthya Karyakram program of India for the early identification of children with NDD.

Sociocultural and drug-related factors associated with adherence to iron-folic acid supplementation among pregnant women - A mixed-methods study.

BACKGROUND: The National Family Health Survey of India (NFHS-5) revealed a lapse in the advancement of mitigating anemia despite free supplementation of iron-folic acid tablets (IFAT) and improvement in IFAT coverage during pregnancy. The local sociocultural beliefs and community perspective toward IFAT are pivotal in reducing the gap between IFAT coverage and consumption. Hence, we proposed the study to assess adherence to IFAT among rural pregnant women and explore the associated factors. MATERIALS AND METHODS: The present study was conducted as a mixed-methods study with a sequential exploratory design in a rural setting of the Model Rural Health Research Unit (MRHRU) from October 2020 to May 2021. Ten focus group discussions (FGDs; 8 - antenatal women, 1 - mother/mother-in-law, and 1 - health care worker) were conducted, and framework analysis was done to identify themes followed by a quantitative survey with a semi-structured questionnaire among antenatal women (n = 236). Logistic regression was used to analyze factors associated with adherence. RESULTS: The major themes that emerged from FGDs were the sociocultural factors (gender norms, communal fallacies), lack of awareness, and drug-related factors (unpalatability, misperceptions, and experienced side effects). Around 57% were adherent to IFAT. Side effects experienced on IFAT intake (P = 0.001, OR = 2.33), misconceptions regarding IFAT, like weight gain in IFAT use (P = 0.001, OR = 2.86), a big baby with IFAT use (P = 0.000, OR = 5.93) negatively influenced adherence. CONCLUSIONS: The significant gaps between IFAT coverage and consumption surrounded the unpleasant odor and stench of IFAT, side effects, lack of individualized counseling, and misperceptions regarding IFAT use.

Psychosocial Problems of Rural Indian Women Practising Breast Self-Examination - a Community-Based Study from Southern India.

Introduction: Globally, breast cancer affects 2.5 million people annually. Younger women with advanced-stage cancers had a lower survival rate, but early detection enhanced survival chances by 27 to 47%. Breast self-examination (BSE) has led to early detection and higher rates of benign biopsies. Studies evaluating the psychosocial impact of BSE are few in India which has been attempted in the present study. Methods: The community-based descriptive cross-sectional study was conducted among rural women aged 30 years and above, who have done BSE at least once without present or prior breast abnormalities in the field practice area of Model Rural Health Research Unit, Tirunelveli. The research questionnaire was developed based on the findings of focus group discussion (FGD) on the same objective in the study area. Results: Among 379 participants, 146 (38.5%) felt confident in their BSE knowledge, 28.2% (n=107) and 5.5% (n=21) of the respondents experienced anxiety and depression while practising BSE, respectively. There is a significant difference between the mean anxiety levels (p-value=0.002) and depression (p-value=0.013) of individuals who have detected anomalies during BSE and those who have not. Conclusion: Regular counselling has to improve knowledge about BSE, like the timing and method of examination, and decreases the anxiety and depression level.

Pharmacogenomic landscape of COVID-19 therapies from Indian population genomes.

Aim: Numerous drugs are being widely prescribed for COVID-19 treatment without any direct evidence for the drug safety/efficacy in patients across diverse ethnic populations. Materials & methods: We analyzed whole genomes of 1029 Indian individuals (IndiGen) to understand the extent of drug-gene (pharmacogenetic), drug-drug and drug-drug-gene interactions associated with COVID-19 therapy in the Indian population. Results: We identified 30 clinically significant pharmacogenetic variants and 73 predicted deleterious pharmacogenetic variants. COVID-19-associated pharmacogenes were substantially overlapped with those of metabolic disorder therapeutics. CYP3A4, ABCB1 and ALB are the most shared pharmacogenes. Fifteen COVID-19 therapeutics were predicted as likely drug-drug interaction candidates when used with four CYP inhibitor drugs. Conclusion: Our findings provide actionable insights for future validation studies and improved clinical decisions for COVID-19 therapy in Indians.

Genetic epidemiology of autoinflammatory disease variants in Indian population from 1029 whole genomes.

BACKGROUND: Autoinflammatory disorders are the group of inherited inflammatory disorders caused due to the genetic defect in the genes that regulates innate immune systems. These have been clinically characterized based on the duration and occurrence of unprovoked fever, skin rash, and patient's ancestry. There are several autoinflammatory disorders that are found to be prevalent in a specific population and whose disease genetic epidemiology within the population has been well understood. However, India has a limited number of genetic studies reported for autoinflammatory disorders till date. The whole genome sequencing and analysis of 1029 Indian individuals performed under the IndiGen project persuaded us to perform the genetic epidemiology of the autoinflammatory disorders in India. RESULTS: We have systematically annotated the genetic variants of 56 genes implicated in autoinflammatory disorder. These genetic variants were reclassified into five categories (i.e., pathogenic, likely pathogenic, benign, likely benign, and variant of uncertain significance (VUS)) according to the American College of Medical Genetics and Association of Molecular pathology (ACMG-AMP) guidelines. Our analysis revealed 20 pathogenic and likely pathogenic variants with significant differences in the allele frequency compared with the global population. We also found six causal founder variants in the IndiGen dataset belonging to different ancestry. We have performed haplotype prediction analysis for founder mutations haplotype that reveals the admixture of the South Asian population with other populations. The cumulative carrier frequency of the autoinflammatory disorder in India was found to be 3.5% which is much higher than reported. CONCLUSION: With such frequency in the Indian population, there is a great need for awareness among clinicians as well as the general public regarding the autoinflammatory disorder. To the best of our knowledge, this is the first and most comprehensive population scale genetic epidemiological study being reported from India.

Methodology for Development of a Community Level Intervention Module for Physical Illness in Persons with Mental Illness (CLIPMI).

BACKGROUND AND OBJECTIVES: Medical illnesses seen in persons with psychiatric disorders are important but often ignored causes of increased morbidity and mortality. Hence, a community level intervention program addressing the issue is proposed. MATERIALS AND METHODS: Patients with severe mental illnesses will be identified by a door-to-door survey and assessed for comorbid physical illnesses like anemia, hypertension, diabetes, and so on. They will then be randomized into two groups. The treatment as usual (TAU) group will not receive intervention from the trained community level workers, while the Intervention group will receive it. RESULTS: The two groups will be compared for the prevalence and severity of comorbid physical illnesses. The expected outcome is compared to the TAU group, the intervention group will have a greater reduction in the morbidity due to physical illnesses and improved mental health. CONCLUSION: If successful, the module can be incorporated into the community level mental health delivery system of the District Mental Health Program (DMHP).