Evidence map›Paper›PMID 33770507›Full record

ArticleAmerican journal of human genetics2021

Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations.

Alicia R Martin, Elizabeth G Atkinson, Sinéad B Chapman, Anne Stevenson, Rocky E Stroud, Tamrat Abebe, Dickens Akena, Melkam Alemayehu, Fred K Ashaba, Lukoye Atwoli and 30 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
15.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 120 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors at 10 institutions in 7 countries.

Alicia R MartinAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: armartin@broadinstitute.org.
Elizabeth G AtkinsonAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Sinéad B ChapmanStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Anne StevensonStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Rocky E StroudStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Tamrat AbebeDepartment of Microbiology, Immunology, and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Dickens AkenaDepartment of Psychiatry, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
Melkam AlemayehuDepartment of Psychiatry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Fred K AshabaDepartment of Immunology & Molecular Biology, College of Health Sciences, Makerere University, Kampala, Uganda.
Lukoye AtwoliDepartment of Mental Health, School of Medicine, Moi University College of Health Sciences, Eldoret, Kenya.
Tera BowersBroad Genomics, Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, MA 02141, USA.
Lori B ChibnikStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
Mark J DalyAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Institute for Molecular Medicine Finland, Helsinki 00014, Finland.
Timothy DeSmetBroad Genomics, Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, MA 02141, USA.
Sheila DodgeBroad Genomics, Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, MA 02141, USA.
Abebaw FekaduDepartment of Psychiatry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Centre for Innovative Drug Development & Therapeutic Trials for Africa, Addis Ababa University, Addis Ababa, Ethiopia.
Steven FerrieraBroad Genomics, Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, MA 02141, USA.
Bizu GelayeDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Stella GichuruDepartment of Mental Health, Moi Teaching and Referral Hospital, Eldoret, Kenya.
Wilfred E InjeraDepartment of Immunology, School of Medicine, Moi University College of Health Sciences, Eldoret, Kenya.
Roxanne JamesDepartment of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
Symon M KariukiNeurosciences Unit, Clinical Department, KEMRI-Wellcome Trust Research Programme-Coast, Kilifi, Kenya; Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK.
Gabriel KigenDepartment of Pharmacology and Toxicology, School of Medicine, Moi University College of Health Sciences, Eldoret, Kenya.
Karestan C KoenenStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Edith KwobahDepartment of Mental Health, Moi Teaching and Referral Hospital, Eldoret, Kenya.
Joseph KyebuzibwaDepartment of Psychiatry, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
Lerato MajaraDepartment of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; SA MRC Human Genetics Research Unit, Division of Human Genetics, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa.
Henry MusinguziDepartment of Immunology & Molecular Biology, College of Health Sciences, Makerere University, Kampala, Uganda.
Rehema M MwemaNeurosciences Unit, Clinical Department, KEMRI-Wellcome Trust Research Programme-Coast, Kilifi, Kenya.
Benjamin M NealeAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Carter P NewmanStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Charles R J C NewtonNeurosciences Unit, Clinical Department, KEMRI-Wellcome Trust Research Programme-Coast, Kilifi, Kenya; Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK.
Joseph K PickrellGencove, Inc., New York, NY 10016, USA.
Raj RamesarSA MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Welelta ShiferawDepartment of Microbiology, Immunology, and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Dan J SteinDepartment of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; SA MRC Unit on Risk & Resilience in Mental Disorders, University of Cape Town and Neuroscience Institute, Cape Town, South Africa.
Solomon TeferraDepartment of Psychiatry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Celia van der MerweAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
Zukiswa ZingelaDepartment of Psychiatry and Human Behavioral Sciences, Walter Sisulu University, Mthatha, South Africa.
NeuroGAP-Psychosis Study Team
Broad Institute · USAddis Ababa University · ETMoi University · KEMakerere University · UGKenya Medical Research Institute · KESouth African Medical Research Council · ZAGenVec · USHarvard University · USUniversity of Cape Town · ZAWalter Sisulu University · ZA

Funding

Training Program in Psychiatric Genetics and Translational ResearchT32MH017119 · NIMH · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI KARESTAN C KOENEN, Jukka-Pekka Onnela · 1985 to 2026
$8.9M
2/4 Powering Genetic Discovery for Severe Mental Illness in Latin American and African AncestriesU01MH125045 · NIMH · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI KOENEN, KARESTAN C · 2020 to 2024
$3.1M
Psychosis Genetics Research in Africa: Building Capacity by Investing in PeopleR01MH120642 · NIMH · BROAD INSTITUTE, INC. · PI AKENA, DICKENS HOWARD, CHIBNIK, LORI BETH · 2019 to 2023
$3.1M
Generalizing polygenic risk prediction methods across populations for insights into psychiatric diseaseR00MH117229 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI MARTIN, ALICIA · 2020 to 2022
$724k
A framework enabling the genomic analysis of psychiatric traits across admixed populations.K01MH121659 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI ATKINSON, ELIZABETH GRACE · 2019 to 2022
$719k
Medical Research Council MR/M025470/1NIMH NIH HHS K01 MH121659NIMH NIH HHS R00 MH117229NIMH NIH HHS R01 MH120642NIMH NIH HHS T32 MH017119NIMH NIH HHS U01 MH125045
6 · The paper itself

Abstract

Genetic studies in underrepresented populations identify disproportionate numbers of novel associations. However, most genetic studies use genotyping arrays and sequenced reference panels that best capture variation most common in European ancestry populations. To compare data generation strategies best suited for underrepresented populations, we sequenced the whole genomes of 91 individuals to high coverage as part of the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study with participants from Ethiopia, Kenya, South Africa, and Uganda. We used a downsampling approach to evaluate the quality of two cost-effective data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole-genome sequencing data. We show that low-coverage sequencing at a depth of ≥4× captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1×) performed comparably to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation; 4× sequencing detects 45% of singletons and 95% of common variants identified in high-coverage African whole genomes. Low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, effectively identify novel variation particularly in underrepresented populations, and present opportunities to enhance variant discovery at a cost similar to traditional approaches.

Indexed as

AfricaDNA Mutational AnalysisGenetics, PopulationGenetic VariationGenome, HumanGenome-Wide Association StudyHealth EquityHumansMicrobiotaWhole Genome SequencingAfricacost comparisonGWASGWAS arrayslow-coverage sequencingstudy designwhole-genome sequencing

Identifiers

PMID33770507
PMCPMC8059370
OpenAlexW3139043797

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.