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المؤلفAbouhashem, Nadien
المؤلفZaied, Roan E.
المؤلفAl-Shafai, Kholoud
المؤلفNofal, Mariam
المؤلفSyed, Najeeb
المؤلفAl-Shafai, Mashael
تاريخ الإتاحة2023-09-20T08:47:09Z
تاريخ النشر2022
اسم المنشورObesity Facts
المصدرScopus
الرقم المعياري الدولي للكتاب16624025
معرّف المصادر الموحدhttp://dx.doi.org/10.1159/000521851
معرّف المصادر الموحدhttp://hdl.handle.net/10576/47779
الملخصIntroduction: Monogenic obesity (MO) is a rare genetic disease characterized by severe early-onset obesity in affected individuals. Previous genetic studies revealed 8 definitive genes for monogenic non-syndromic obesity; many were discovered in consanguineous populations. Here, we examined MO in the Qatari population, whose population is largely consanguineous (54%) and characterized by extensive obesity (45%). Methods: Whole genome sequencing data of Qatar Biobank samples from 250 subjects with obesity and 250 subjects with normal weight, obtained in association with the Qatar Genome Programme, were searched for genetic variants in the genes known to be associated with MO (i.e., LEP, LEPR, POMC, PCSK1, MC3R, MC4R, MRAP2, and ADCY3). The impact of the variants identified was investigated utilizing in silico tools for prediction in combination with protein visualization by PyMOL. Results: We identified potential MO variants in more than 5% of the cases in our cohort. We revealed 11 rare variants in 6 of the genes targeted, including two disease-causing variants in MC4R and MRAP2, all of which were heterozygous. Moreover, enrichment of a heterozygous ADCY3 variant (c.1658C>T; p.A553V) appeared to cause severe obesity in an autosomal dominant manner. Conclusion: These findings highlight the importance of implementing routine testing for genetic variants that predispose for MO in Qatar. Clearly, additional studies of this nature on populations not yet examined are required. At the same time, functional investigations, both in vitro and in vivo, are necessary in order to better understand the role of the variants identified in the pathogenesis of obesity.
راعي المشروعThis study was supported by Qatar University (internal grant # QUCP-CHS-2018/2019-1). The authors are solely responsible for the findings reported. We wish to thank the QBB and QGP for giving us access to the phenotypic and whole genome sequencing data which made this study possible, with special thanks to Dr. Nahla Afifi, the director of QBB, Dr. Said Ismail, the director of QGP, and Prof. Asma Al-Thani, the Chair of the National Genome Committee. We also thank the QBB participants for donating their samples and allowing their data to be utilized for research purposes.
اللغةen
الناشرS. Karger AG
الموضوعConsanguinity
Monogenic obesity
Qatar Biobank
Qatar Genome Programme
Rare variants
العنوانThe Spectrum of Genetic Variants Associated with the Development of Monogenic Obesity in Qatar
النوعArticle
الصفحات357-365
رقم العدد3
رقم المجلد15
dc.accessType Open Access


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