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...

Descripción completa

Detalles Bibliográficos
Autores principales: Rajcsanyi, Luisa Sophie, Zheng, Yiran, Fischer-Posovszky, Pamela, Wabitsch, Martin, Hebebrand, Johannes, Hinney, Anke
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