Evidence map›Paper›PMID 42136028›Full record

ArticleHGG advances2026

Burden of heterozygote carriers for autosomal recessive conditions in the Middle East: A study of 14,392 genomes.

Esther Nkrumah, Hajer Al-Mulla, Aryan Bashar, Vishal Soman, Chadi Saad, John Wang, Helia Darabi, Svetlana A Yatsenko, Aleksandar Rajkovic, Uma Chandran and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in HGG advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Esther NkrumahJoan H. Marks Graduate Program in Human Genetics, Sarah Lawrence College, Bronxville, NY 10708, USA.
Hajer Al-MullaJoan H. Marks Graduate Program in Human Genetics, Sarah Lawrence College, Bronxville, NY 10708, USA.
Aryan BasharData Science Graduate Program, University of Colorado Boulder, Boulder, CO, USA.
Vishal SomanDepartment of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Chadi SaadQatar Genome, Qatar Precision Health Institute, Qatar Foundation, Doha 5825, Qatar; Development and Innovation, Qatar Foundation, Doha, Qatar.
John WangDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Helia DarabiMedical Genetics and Genomics Laboratories, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Svetlana A YatsenkoDepartment of Pathology, Stanford University, Stanford, CA, USA.
Aleksandar RajkovicDepartment of Pathology, University of California, San Francisco, San Francisco, CA, USA; Institute of Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Uma ChandranDepartment of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Hamdi MbarekQatar Genome, Qatar Precision Health Institute, Qatar Foundation, Doha 5825, Qatar; Development and Innovation, Qatar Foundation, Doha, Qatar.
Mahmoud AarabiMedical Genetics and Genomics Laboratories, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Departments of Pathology, and Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: mahmoud.aarabi@pitt.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The American College of Medical Genetics and Genomics (ACMG) recommends Tier-3 reproductive carrier screening for 97 genes associated with autosomal recessive (AR) conditions (AR genes). Gene selection for screening is based on a gene carrier frequency (GCF) of ≥1/200 in the Genome Aggregation Database (gnomAD)v2 populations and disease severity. The utility of ACMG Tier 3 in the Middle Eastern population is unclear as this ancestral group was not represented in the gnomADv2. We utilized genome data from 14,392 individuals in the Qatar Genome Project to estimate the carrier frequency of AR conditions in the Middle Eastern population. The frequency of 136,624 pathogenic/likely pathogenic variants in 2,987 AR genes from ClinVar was analyzed to estimate the GCF in the Qatari cohort. Genes with GCF ≥ 1/200 were curated by an expert panel for the severity of corresponding conditions. We identified 69 genes with GCF ≥ 1/200 associated with moderate to profound clinical presentations, 53 of which were unique to the Middle Eastern population. Common variants were observed with high frequency for individual genes such as IL2RA that suggested the presence of founder effects not described previously. Simulation studies predicted that inclusion of the ancestry-specific genes increased the chance of detecting at-risk couples from 3.85% to 8.15% in the Middle Eastern population. This study highlights the limitations of relying on global datasets to accurately identify the candidate genes for carrier screening in different populations. Our findings provide a framework for targeted, population-specific carrier-screening programs in regions not represented in the large genome datasets.

Indexed as

Genes, RecessiveGenetic Carrier ScreeningGenome, HumanHeterozygoteGene FrequencyGenetic TestingHumansMiddle EastMiddle Eastern PeopleQatarancestryautosomal recessivecarrier screeninggenome sequencinggnomADIL2RA geneMiddle Easternprenatal geneticsQatar

Identifiers

PMID42136028
PMCPMC13254388

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.