Ancestral risk modification for multiple sclerosis susceptibility detected across the Major Histocompatibility Complex in a multi-ethnic population.
The Major Histocompatibility Complex (MHC) makes the largest genetic contribution to multiple sclerosis (MS) susceptibility, with 32 independent effects across the region explaining 20% of the heritability in European populations. Variation is high across populations with allele frequency difference...
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279132&type=printable |
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| author | Ashley H Beecham Lilyana Amezcua Angel Chinea Clara P Manrique Lissette Gomez Andrea Martinez Gary W Beecham Nikolaos A Patsopoulos Tanuja Chitnis Howard L Weiner Philip L De Jager Esteban G Burchard Brett T Lund Kathryn C Fitzgerald Peter A Calabresi Silvia R Delgado Jorge R Oksenberg Jacob L McCauley |
| author_facet | Ashley H Beecham Lilyana Amezcua Angel Chinea Clara P Manrique Lissette Gomez Andrea Martinez Gary W Beecham Nikolaos A Patsopoulos Tanuja Chitnis Howard L Weiner Philip L De Jager Esteban G Burchard Brett T Lund Kathryn C Fitzgerald Peter A Calabresi Silvia R Delgado Jorge R Oksenberg Jacob L McCauley |
| author_sort | Ashley H Beecham |
| collection | DOAJ |
| description | The Major Histocompatibility Complex (MHC) makes the largest genetic contribution to multiple sclerosis (MS) susceptibility, with 32 independent effects across the region explaining 20% of the heritability in European populations. Variation is high across populations with allele frequency differences and population-specific risk alleles identified. We sought to identify MHC-specific MS susceptibility variants and assess the effect of ancestral risk modification within 2652 Latinx and Hispanic individuals as well as 2435 Black and African American individuals. We have identified several novel susceptibility alleles which are rare in European populations including HLA-B*53:01, and we have utilized the differing linkage disequilibrium patterns inherent to these populations to identify an independent role for HLA-DRB1*15:01 and HLA-DQB1*06:02 on MS risk. We found a decrease in Native American ancestry in MS cases vs controls across the MHC, peaking near the previously identified MICB locus with a decrease of ~5.5% in Hispanics and ~0.4% in African Americans. We have identified several susceptibility variants, including within the MICB gene region, which show global ancestry risk modification and indicate ancestral differences which may be due in part to correlated environmental factors. We have also identified several susceptibility variants for which MS risk is modified by local ancestry and indicate true ancestral genetic differences; including HLA-DQB1*06:02 for which MS risk for European allele carriers is almost two times the risk for African allele carriers. These results validate the importance of investigating MS susceptibility at an ancestral level and offer insight into the epidemiology of MS phenotypic diversity. |
| format | Article |
| id | doaj-art-2a71d7c0f97a4ee9840c19b2575059f4 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-2a71d7c0f97a4ee9840c19b2575059f42025-08-20T03:46:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011712e027913210.1371/journal.pone.0279132Ancestral risk modification for multiple sclerosis susceptibility detected across the Major Histocompatibility Complex in a multi-ethnic population.Ashley H BeechamLilyana AmezcuaAngel ChineaClara P ManriqueLissette GomezAndrea MartinezGary W BeechamNikolaos A PatsopoulosTanuja ChitnisHoward L WeinerPhilip L De JagerEsteban G BurchardBrett T LundKathryn C FitzgeraldPeter A CalabresiSilvia R DelgadoJorge R OksenbergJacob L McCauleyThe Major Histocompatibility Complex (MHC) makes the largest genetic contribution to multiple sclerosis (MS) susceptibility, with 32 independent effects across the region explaining 20% of the heritability in European populations. Variation is high across populations with allele frequency differences and population-specific risk alleles identified. We sought to identify MHC-specific MS susceptibility variants and assess the effect of ancestral risk modification within 2652 Latinx and Hispanic individuals as well as 2435 Black and African American individuals. We have identified several novel susceptibility alleles which are rare in European populations including HLA-B*53:01, and we have utilized the differing linkage disequilibrium patterns inherent to these populations to identify an independent role for HLA-DRB1*15:01 and HLA-DQB1*06:02 on MS risk. We found a decrease in Native American ancestry in MS cases vs controls across the MHC, peaking near the previously identified MICB locus with a decrease of ~5.5% in Hispanics and ~0.4% in African Americans. We have identified several susceptibility variants, including within the MICB gene region, which show global ancestry risk modification and indicate ancestral differences which may be due in part to correlated environmental factors. We have also identified several susceptibility variants for which MS risk is modified by local ancestry and indicate true ancestral genetic differences; including HLA-DQB1*06:02 for which MS risk for European allele carriers is almost two times the risk for African allele carriers. These results validate the importance of investigating MS susceptibility at an ancestral level and offer insight into the epidemiology of MS phenotypic diversity.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279132&type=printable |
| spellingShingle | Ashley H Beecham Lilyana Amezcua Angel Chinea Clara P Manrique Lissette Gomez Andrea Martinez Gary W Beecham Nikolaos A Patsopoulos Tanuja Chitnis Howard L Weiner Philip L De Jager Esteban G Burchard Brett T Lund Kathryn C Fitzgerald Peter A Calabresi Silvia R Delgado Jorge R Oksenberg Jacob L McCauley Ancestral risk modification for multiple sclerosis susceptibility detected across the Major Histocompatibility Complex in a multi-ethnic population. PLoS ONE |
| title | Ancestral risk modification for multiple sclerosis susceptibility detected across the Major Histocompatibility Complex in a multi-ethnic population. |
| title_full | Ancestral risk modification for multiple sclerosis susceptibility detected across the Major Histocompatibility Complex in a multi-ethnic population. |
| title_fullStr | Ancestral risk modification for multiple sclerosis susceptibility detected across the Major Histocompatibility Complex in a multi-ethnic population. |
| title_full_unstemmed | Ancestral risk modification for multiple sclerosis susceptibility detected across the Major Histocompatibility Complex in a multi-ethnic population. |
| title_short | Ancestral risk modification for multiple sclerosis susceptibility detected across the Major Histocompatibility Complex in a multi-ethnic population. |
| title_sort | ancestral risk modification for multiple sclerosis susceptibility detected across the major histocompatibility complex in a multi ethnic population |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279132&type=printable |
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