Cargando…
Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus
INTRODUCTION: We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to deve...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095681/ https://www.ncbi.nlm.nih.gov/pubmed/24946689 http://dx.doi.org/10.1186/ar4585 |
_version_ | 1782326076120236032 |
---|---|
author | Alonso-Perez, Elisa Suarez-Gestal, Marian Calaza, Manuel Blanco, Francisco J Suarez, Ana Santos, Maria Jose Papasteriades, Chryssa Carreira, Patricia Pullmann, Rudolf Ordi-Ros, Josep Marchini, Maurizio Skopouli, Fotini N Bijl, Marc Barrizone, Nadia Sebastiani, Gian Domenico Migliaresi, Sergio Witte, Torsten Lauwerys, Bernard R Kovacs, Attila Ruzickova, Sarka Gomez-Reino, Juan J Gonzalez, Antonio |
author_facet | Alonso-Perez, Elisa Suarez-Gestal, Marian Calaza, Manuel Blanco, Francisco J Suarez, Ana Santos, Maria Jose Papasteriades, Chryssa Carreira, Patricia Pullmann, Rudolf Ordi-Ros, Josep Marchini, Maurizio Skopouli, Fotini N Bijl, Marc Barrizone, Nadia Sebastiani, Gian Domenico Migliaresi, Sergio Witte, Torsten Lauwerys, Bernard R Kovacs, Attila Ruzickova, Sarka Gomez-Reino, Juan J Gonzalez, Antonio |
author_sort | Alonso-Perez, Elisa |
collection | PubMed |
description | INTRODUCTION: We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE. METHODS: Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRS(s)). RESULTS: Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRS(s). GRS(s) were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P < 10(−16)) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10(−7)), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results. CONCLUSION: Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women. |
format | Online Article Text |
id | pubmed-4095681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40956812014-07-14 Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus Alonso-Perez, Elisa Suarez-Gestal, Marian Calaza, Manuel Blanco, Francisco J Suarez, Ana Santos, Maria Jose Papasteriades, Chryssa Carreira, Patricia Pullmann, Rudolf Ordi-Ros, Josep Marchini, Maurizio Skopouli, Fotini N Bijl, Marc Barrizone, Nadia Sebastiani, Gian Domenico Migliaresi, Sergio Witte, Torsten Lauwerys, Bernard R Kovacs, Attila Ruzickova, Sarka Gomez-Reino, Juan J Gonzalez, Antonio Arthritis Res Ther Research Article INTRODUCTION: We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE. METHODS: Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRS(s)). RESULTS: Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRS(s). GRS(s) were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P < 10(−16)) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10(−7)), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results. CONCLUSION: Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women. BioMed Central 2014 2014-06-19 /pmc/articles/PMC4095681/ /pubmed/24946689 http://dx.doi.org/10.1186/ar4585 Text en Copyright © 2014 Alonso-Perez et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Alonso-Perez, Elisa Suarez-Gestal, Marian Calaza, Manuel Blanco, Francisco J Suarez, Ana Santos, Maria Jose Papasteriades, Chryssa Carreira, Patricia Pullmann, Rudolf Ordi-Ros, Josep Marchini, Maurizio Skopouli, Fotini N Bijl, Marc Barrizone, Nadia Sebastiani, Gian Domenico Migliaresi, Sergio Witte, Torsten Lauwerys, Bernard R Kovacs, Attila Ruzickova, Sarka Gomez-Reino, Juan J Gonzalez, Antonio Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus |
title | Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus |
title_full | Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus |
title_fullStr | Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus |
title_full_unstemmed | Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus |
title_short | Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus |
title_sort | lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095681/ https://www.ncbi.nlm.nih.gov/pubmed/24946689 http://dx.doi.org/10.1186/ar4585 |
work_keys_str_mv | AT alonsoperezelisa lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT suarezgestalmarian lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT calazamanuel lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT blancofranciscoj lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT suarezana lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT santosmariajose lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT papasteriadeschryssa lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT carreirapatricia lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT pullmannrudolf lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT ordirosjosep lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT marchinimaurizio lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT skopoulifotinin lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT bijlmarc lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT barrizonenadia lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT sebastianigiandomenico lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT migliaresisergio lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT wittetorsten lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT lauwerysbernardr lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT kovacsattila lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT ruzickovasarka lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT gomezreinojuanj lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus AT gonzalezantonio lackofreplicationofhighergeneticriskloadinmenthaninwomenwithsystemiclupuserythematosus |