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Record W4379878818 · doi:10.1038/s41467-023-38766-1

South Asian medical cohorts reveal strong founder effects and high rates of homozygosity

2023· article· en· W4379878818 on OpenAlexaff
Jeffrey D. Wall, J. Fah Sathirapongsasuti, Ravi Gupta, Asif Rasheed, Venkatesan Radha, Saurabh Belsare, Ramesh Menon, Sameer Phalke, Anuradha Mittal, John Fang, Deepak Tanneeru, Manjari Deshmukh, Akshi Bassi, Jacqueline A. Robinson, Ruchi Chaudhary, Sakthivel Murugan, Zameer ul-Asar, Imran Saleem, Unzila Ishtiaq, Areej Fatima, Saqib Shafi Sheikh, Shahid Hameed, Mohammad Ishaq, Syed Zahed Rasheed, Fazal-ur-Rehman Memon, Anjum Jalal, Shahid Abbas, Philippe Frossard, Christian Fuchsberger, Lukas Forer, Sebastian Schoenherr, Qixin Bei, Tushar Bhangale, Jennifer Tom, Santosh Gopi Krishna Gadde, BV Priya, Naveen Naik, Minxian Wang, Pui–Yan Kwok, Amit V. Khera, B. R. Lakshmi, Adam S. Butterworth, Rajiv Chowdhury, John Danesh, Emanuele Di Angelantonio, Aliya Naheed, Vinay Goyal, Rukmini Mridula Kandadai, Hrishikesh Kumar, Rupam Borgohain, Adreesh Mukherjee, Pettarusp M. Wadia, Ravi Yadav, Soaham Desai, Niraj Kumar, Atanu Biswas, Pramod Kumar Pal, Uday B. Muthane, Shymal K. Das, Vedam L. Ramprasad, Prashanth Lingappa Kukkle, Somasekar Seshagiri, Sekar Kathiresan, Arkasubhra Ghosh, Viswanathan Mohan, Danish Saleheen, Eric Stawiski, Andrew S. Peterson

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsParkinson's Clinic of Eastern Toronto & Movement Disorders Centre
FundersNational Human Genome Research InstituteMedical Research CouncilNational Institute for Health and Care Research
KeywordsFounder effectConsanguinityGenotypingWhole genome sequencingInbreedingPopulationBiologyEvolutionary biologyPopulation geneticsSouth asiaEndogamyImputation (statistics)GeneticsDemographyGenomeMedicineGenotypeEnvironmental healthGeneMissing data

Abstract

fetched live from OpenAlex

The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.002
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0050.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.319
Teacher spread0.304 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations38
Published2023
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicGenetic Associations and EpidemiologyFrench-language works237,207