Cargando…
Prevalence estimates of putatively pathogenic leptin variants in the gnomAD database
Homozygosity for pathogenic variants in the leptin gene leads to congenital leptin deficiency causing severe early-onset obesity. This monogenic form of obesity has mainly been detected in patients from consanguineous families. Prevalence estimates for the general population using the Exome Aggregat...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484668/ https://www.ncbi.nlm.nih.gov/pubmed/36121795 http://dx.doi.org/10.1371/journal.pone.0266642 |
_version_ | 1784791922692325376 |
---|---|
author | Rajcsanyi, Luisa Sophie Zheng, Yiran Fischer-Posovszky, Pamela Wabitsch, Martin Hebebrand, Johannes Hinney, Anke |
author_facet | Rajcsanyi, Luisa Sophie Zheng, Yiran Fischer-Posovszky, Pamela Wabitsch, Martin Hebebrand, Johannes Hinney, Anke |
author_sort | Rajcsanyi, Luisa Sophie |
collection | PubMed |
description | Homozygosity for pathogenic variants in the leptin gene leads to congenital leptin deficiency causing severe early-onset obesity. This monogenic form of obesity has mainly been detected in patients from consanguineous families. Prevalence estimates for the general population using the Exome Aggregation Consortium (ExAC) database reported a low frequency of leptin mutations. One in approximately 15 million individuals will be homozygous for a deleterious leptin variant. With the present study, we aimed to extend these findings utilizing the augmented Genome Aggregation Database (gnomAD) v2.1.1 including more than 140,000 samples. In total, 68 non-synonymous and 7 loss-of-function leptin variants were deposited in gnomAD. By predicting functional implications with the help of in silico tools, like SIFT, PolyPhen2 and MutationTaster2021, the prevalence of hetero- and homozygosity for putatively pathogenic variants (n = 32; pathogenic prediction by at least two tools) in the leptin gene were calculated. Across all populations, the estimated prevalence for heterozygosity for functionally relevant variants was approximately 1:2,100 and 1:17,830,000 for homozygosity. This prevalence deviated between the individual populations. Accordingly, people from East Asia and individuals of mixed ethnicities (‘Others’) were at greater risk to carry a possibly damaging leptin variant. Generally, this study emphasises the scarcity of pathogenic leptin variants in the general population with varying prevalence for distinct study groups. |
format | Online Article Text |
id | pubmed-9484668 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-94846682022-09-20 Prevalence estimates of putatively pathogenic leptin variants in the gnomAD database Rajcsanyi, Luisa Sophie Zheng, Yiran Fischer-Posovszky, Pamela Wabitsch, Martin Hebebrand, Johannes Hinney, Anke PLoS One Research Article Homozygosity for pathogenic variants in the leptin gene leads to congenital leptin deficiency causing severe early-onset obesity. This monogenic form of obesity has mainly been detected in patients from consanguineous families. Prevalence estimates for the general population using the Exome Aggregation Consortium (ExAC) database reported a low frequency of leptin mutations. One in approximately 15 million individuals will be homozygous for a deleterious leptin variant. With the present study, we aimed to extend these findings utilizing the augmented Genome Aggregation Database (gnomAD) v2.1.1 including more than 140,000 samples. In total, 68 non-synonymous and 7 loss-of-function leptin variants were deposited in gnomAD. By predicting functional implications with the help of in silico tools, like SIFT, PolyPhen2 and MutationTaster2021, the prevalence of hetero- and homozygosity for putatively pathogenic variants (n = 32; pathogenic prediction by at least two tools) in the leptin gene were calculated. Across all populations, the estimated prevalence for heterozygosity for functionally relevant variants was approximately 1:2,100 and 1:17,830,000 for homozygosity. This prevalence deviated between the individual populations. Accordingly, people from East Asia and individuals of mixed ethnicities (‘Others’) were at greater risk to carry a possibly damaging leptin variant. Generally, this study emphasises the scarcity of pathogenic leptin variants in the general population with varying prevalence for distinct study groups. Public Library of Science 2022-09-19 /pmc/articles/PMC9484668/ /pubmed/36121795 http://dx.doi.org/10.1371/journal.pone.0266642 Text en © 2022 Rajcsanyi et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Rajcsanyi, Luisa Sophie Zheng, Yiran Fischer-Posovszky, Pamela Wabitsch, Martin Hebebrand, Johannes Hinney, Anke Prevalence estimates of putatively pathogenic leptin variants in the gnomAD database |
title | Prevalence estimates of putatively pathogenic leptin variants in the gnomAD database |
title_full | Prevalence estimates of putatively pathogenic leptin variants in the gnomAD database |
title_fullStr | Prevalence estimates of putatively pathogenic leptin variants in the gnomAD database |
title_full_unstemmed | Prevalence estimates of putatively pathogenic leptin variants in the gnomAD database |
title_short | Prevalence estimates of putatively pathogenic leptin variants in the gnomAD database |
title_sort | prevalence estimates of putatively pathogenic leptin variants in the gnomad database |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484668/ https://www.ncbi.nlm.nih.gov/pubmed/36121795 http://dx.doi.org/10.1371/journal.pone.0266642 |
work_keys_str_mv | AT rajcsanyiluisasophie prevalenceestimatesofputativelypathogenicleptinvariantsinthegnomaddatabase AT zhengyiran prevalenceestimatesofputativelypathogenicleptinvariantsinthegnomaddatabase AT fischerposovszkypamela prevalenceestimatesofputativelypathogenicleptinvariantsinthegnomaddatabase AT wabitschmartin prevalenceestimatesofputativelypathogenicleptinvariantsinthegnomaddatabase AT hebebrandjohannes prevalenceestimatesofputativelypathogenicleptinvariantsinthegnomaddatabase AT hinneyanke prevalenceestimatesofputativelypathogenicleptinvariantsinthegnomaddatabase |