The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants
<div><p>Approximately 0.5–1.4% of natal males and 0.2–0.3% of natal females meet DSM-5 criteria for gender dysphoria, with many of these individuals self-describing as transgender men or women. Despite recent improvements both in social acceptance of transgender individuals as well as ac...
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| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2019
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| الموضوعات: | |
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إضافة وسم
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| _version_ | 1864513513950543872 |
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| author | J. Graham Theisen (18618646) |
| author2 | Viji Sundaram (18618649) Mary S. Filchak (18618652) Lynn P. Chorich (14776984) Megan E. Sullivan (15016457) James Knight (3664885) Hyung-Goo Kim (728597) Lawrence C. Layman (13913559) |
| author2_role | author author author author author author author |
| author_facet | J. Graham Theisen (18618646) Viji Sundaram (18618649) Mary S. Filchak (18618652) Lynn P. Chorich (14776984) Megan E. Sullivan (15016457) James Knight (3664885) Hyung-Goo Kim (728597) Lawrence C. Layman (13913559) |
| author_role | author |
| dc.creator.none.fl_str_mv | J. Graham Theisen (18618646) Viji Sundaram (18618649) Mary S. Filchak (18618652) Lynn P. Chorich (14776984) Megan E. Sullivan (15016457) James Knight (3664885) Hyung-Goo Kim (728597) Lawrence C. Layman (13913559) |
| dc.date.none.fl_str_mv | 2019-12-27T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41598-019-53500-y |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/The_Use_of_Whole_Exome_Sequencing_in_a_Cohort_of_Transgender_Individuals_to_Identify_Rare_Genetic_Variants/25907575 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Gender Dysphoria Transgender DSM-5 Social Acceptance Gender Affirming Therapy Etiology Genetic Contribution |
| dc.title.none.fl_str_mv | The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <div><p>Approximately 0.5–1.4% of natal males and 0.2–0.3% of natal females meet DSM-5 criteria for gender dysphoria, with many of these individuals self-describing as transgender men or women. Despite recent improvements both in social acceptance of transgender individuals as well as access to gender affirming therapy, progress in both areas has been hampered by poor understanding of the etiology of gender dysphoria. Prior studies have suggested a genetic contribution to gender dysphoria, but previously proposed candidate genes have not yet been verified in follow-up investigation. In this study, we expand on the topic of gender identity genomics by identifying rare variants in genes associated with sexually dimorphic brain development and exploring how they could contribute to gender dysphoria. To accomplish this, we performed whole exome sequencing on the genomic DNA of 13 transgender males and 17 transgender females. Whole exome sequencing revealed 120,582 genetic variants. After filtering, 441 variants in 421 genes remained for further consideration, including 21 nonsense, 28 frameshift, 13 splice-region, and 225 missense variants. Of these, 21 variants in 19 genes were found to have associations with previously described estrogen receptor activated pathways of sexually dimorphic brain development. These variants were confirmed by Sanger Sequencing. Our findings suggest a new avenue for investigation of genes involved in estrogen signaling pathways related to sexually dimorphic brain development and their relationship to gender dysphoria.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<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/10.1038/s41598-019-53500-y" target="_blank">https://dx.doi.org/10.1038/s41598-019-53500-y</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_92e09fb9d5007e1a45d0a95e70ba333a |
| identifier_str_mv | 10.1038/s41598-019-53500-y |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25907575 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic VariantsJ. Graham Theisen (18618646)Viji Sundaram (18618649)Mary S. Filchak (18618652)Lynn P. Chorich (14776984)Megan E. Sullivan (15016457)James Knight (3664885)Hyung-Goo Kim (728597)Lawrence C. Layman (13913559)Biological sciencesGeneticsGender DysphoriaTransgenderDSM-5Social AcceptanceGender Affirming TherapyEtiologyGenetic Contribution<div><p>Approximately 0.5–1.4% of natal males and 0.2–0.3% of natal females meet DSM-5 criteria for gender dysphoria, with many of these individuals self-describing as transgender men or women. Despite recent improvements both in social acceptance of transgender individuals as well as access to gender affirming therapy, progress in both areas has been hampered by poor understanding of the etiology of gender dysphoria. Prior studies have suggested a genetic contribution to gender dysphoria, but previously proposed candidate genes have not yet been verified in follow-up investigation. In this study, we expand on the topic of gender identity genomics by identifying rare variants in genes associated with sexually dimorphic brain development and exploring how they could contribute to gender dysphoria. To accomplish this, we performed whole exome sequencing on the genomic DNA of 13 transgender males and 17 transgender females. Whole exome sequencing revealed 120,582 genetic variants. After filtering, 441 variants in 421 genes remained for further consideration, including 21 nonsense, 28 frameshift, 13 splice-region, and 225 missense variants. Of these, 21 variants in 19 genes were found to have associations with previously described estrogen receptor activated pathways of sexually dimorphic brain development. These variants were confirmed by Sanger Sequencing. Our findings suggest a new avenue for investigation of genes involved in estrogen signaling pathways related to sexually dimorphic brain development and their relationship to gender dysphoria.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<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/10.1038/s41598-019-53500-y" target="_blank">https://dx.doi.org/10.1038/s41598-019-53500-y</a></p>2019-12-27T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-019-53500-yhttps://figshare.com/articles/journal_contribution/The_Use_of_Whole_Exome_Sequencing_in_a_Cohort_of_Transgender_Individuals_to_Identify_Rare_Genetic_Variants/25907575CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259075752019-12-27T03:00:00Z |
| spellingShingle | The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants J. Graham Theisen (18618646) Biological sciences Genetics Gender Dysphoria Transgender DSM-5 Social Acceptance Gender Affirming Therapy Etiology Genetic Contribution |
| status_str | publishedVersion |
| title | The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants |
| title_full | The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants |
| title_fullStr | The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants |
| title_full_unstemmed | The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants |
| title_short | The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants |
| title_sort | The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants |
| topic | Biological sciences Genetics Gender Dysphoria Transgender DSM-5 Social Acceptance Gender Affirming Therapy Etiology Genetic Contribution |