The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects
<p dir="ltr">Familial hypercholesterolemia (FH) is an inherited disease characterized by reduced efficiency of low-density lipoprotein-cholesterol (LDL-C) removal from the blood and, consequently, an increased risk of life-threatening early cardiovascular complications. In Qatar, the...
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| مؤلفون آخرون: | , , , , , , , |
| منشور في: |
2022
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| _version_ | 1864513517537722368 |
|---|---|
| author | Ilhame Diboun (3522413) |
| author2 | Yasser Al-Sarraj (11721425) Salman M. Toor (8854751) Shaban Mohammed (14150130) Nadeem Qureshi (508036) Moza S. H. Al Hail (18282205) Amin Jayyousi (3158868) Jassim Al Suwaidi (284932) Omar M. E. Albagha (11704871) |
| author2_role | author author author author author author author author |
| author_facet | Ilhame Diboun (3522413) Yasser Al-Sarraj (11721425) Salman M. Toor (8854751) Shaban Mohammed (14150130) Nadeem Qureshi (508036) Moza S. H. Al Hail (18282205) Amin Jayyousi (3158868) Jassim Al Suwaidi (284932) Omar M. E. Albagha (11704871) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ilhame Diboun (3522413) Yasser Al-Sarraj (11721425) Salman M. Toor (8854751) Shaban Mohammed (14150130) Nadeem Qureshi (508036) Moza S. H. Al Hail (18282205) Amin Jayyousi (3158868) Jassim Al Suwaidi (284932) Omar M. E. Albagha (11704871) |
| dc.date.none.fl_str_mv | 2022-07-15T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fgene.2022.927504 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/The_Prevalence_and_Genetic_Spectrum_of_Familial_Hypercholesterolemia_in_Qatar_Based_on_Whole_Genome_Sequencing_of_14_000_Subjects/25516549 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology Clinical sciences dyslipidemias hypercholesterolemia familial hypercholesterolemia monogenic FH LDL-C LDLR |
| dc.title.none.fl_str_mv | The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Familial hypercholesterolemia (FH) is an inherited disease characterized by reduced efficiency of low-density lipoprotein-cholesterol (LDL-C) removal from the blood and, consequently, an increased risk of life-threatening early cardiovascular complications. In Qatar, the prevalence of FH has not been determined and the disease, as in many countries, is largely underdiagnosed. In this study, we combined whole-genome sequencing data from the Qatar Genome Program with deep phenotype data from Qatar Biobank for 14,056 subjects to determine the genetic spectrum and estimate the prevalence of FH in Qatar. We used the Dutch Lipid Clinic Network (DLCN) as a diagnostic tool and scrutinized 11 FH-related genes for known pathogenic and possibly pathogenic mutations. Results revealed an estimated prevalence of 0.8% (1:125) for definite/probable cases of FH in the Qatari population. We detected 16 known pathogenic/likely pathogenic mutations in LDLR and one in PCSK9; all in a heterozygous state with high penetrance. The most common mutation was rs1064793799 (c.313+3A >C) followed by rs771019366 (p.Asp90Gly); both in LDLR. In addition, we identified 18 highly penetrant possibly pathogenic variants, of which 5 were Qatari-specific, in LDLR, APOB, PCSK9 and APOE, which are predicted to be among the top 1% most deleterious mutations in the human genome but further validations are required to confirm their pathogenicity. We did not detect any homozygous FH or autosomal recessive mutations in our study cohort. This pioneering study provides a reliable estimate of FH prevalence in Qatar based on a significantly large population-based cohort, whilst uncovering the spectrum of genetic variants associated with FH.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Genetics<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fgene.2022.927504" target="_blank">https://dx.doi.org/10.3389/fgene.2022.927504</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_d101bec102eb1952975e766aeb54300c |
| identifier_str_mv | 10.3389/fgene.2022.927504 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25516549 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 SubjectsIlhame Diboun (3522413)Yasser Al-Sarraj (11721425)Salman M. Toor (8854751)Shaban Mohammed (14150130)Nadeem Qureshi (508036)Moza S. H. Al Hail (18282205)Amin Jayyousi (3158868)Jassim Al Suwaidi (284932)Omar M. E. Albagha (11704871)Biological sciencesGeneticsBiomedical and clinical sciencesCardiovascular medicine and haematologyClinical sciencesdyslipidemiashypercholesterolemiafamilial hypercholesterolemiamonogenicFHLDL-CLDLR<p dir="ltr">Familial hypercholesterolemia (FH) is an inherited disease characterized by reduced efficiency of low-density lipoprotein-cholesterol (LDL-C) removal from the blood and, consequently, an increased risk of life-threatening early cardiovascular complications. In Qatar, the prevalence of FH has not been determined and the disease, as in many countries, is largely underdiagnosed. In this study, we combined whole-genome sequencing data from the Qatar Genome Program with deep phenotype data from Qatar Biobank for 14,056 subjects to determine the genetic spectrum and estimate the prevalence of FH in Qatar. We used the Dutch Lipid Clinic Network (DLCN) as a diagnostic tool and scrutinized 11 FH-related genes for known pathogenic and possibly pathogenic mutations. Results revealed an estimated prevalence of 0.8% (1:125) for definite/probable cases of FH in the Qatari population. We detected 16 known pathogenic/likely pathogenic mutations in LDLR and one in PCSK9; all in a heterozygous state with high penetrance. The most common mutation was rs1064793799 (c.313+3A >C) followed by rs771019366 (p.Asp90Gly); both in LDLR. In addition, we identified 18 highly penetrant possibly pathogenic variants, of which 5 were Qatari-specific, in LDLR, APOB, PCSK9 and APOE, which are predicted to be among the top 1% most deleterious mutations in the human genome but further validations are required to confirm their pathogenicity. We did not detect any homozygous FH or autosomal recessive mutations in our study cohort. This pioneering study provides a reliable estimate of FH prevalence in Qatar based on a significantly large population-based cohort, whilst uncovering the spectrum of genetic variants associated with FH.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Genetics<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fgene.2022.927504" target="_blank">https://dx.doi.org/10.3389/fgene.2022.927504</a></p>2022-07-15T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fgene.2022.927504https://figshare.com/articles/journal_contribution/The_Prevalence_and_Genetic_Spectrum_of_Familial_Hypercholesterolemia_in_Qatar_Based_on_Whole_Genome_Sequencing_of_14_000_Subjects/25516549CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/255165492022-07-15T03:00:00Z |
| spellingShingle | The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects Ilhame Diboun (3522413) Biological sciences Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology Clinical sciences dyslipidemias hypercholesterolemia familial hypercholesterolemia monogenic FH LDL-C LDLR |
| status_str | publishedVersion |
| title | The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects |
| title_full | The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects |
| title_fullStr | The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects |
| title_full_unstemmed | The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects |
| title_short | The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects |
| title_sort | The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects |
| topic | Biological sciences Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology Clinical sciences dyslipidemias hypercholesterolemia familial hypercholesterolemia monogenic FH LDL-C LDLR |