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6. Age-specific reference intervals for TSH and FT4 to optimize diagnosis of thyroid disease

Author

Jansen, Heleen, primary, Dirks, Niek, additional, Hillebrand, Jacquelien, additional, Ten, Boekel Edwin, additional, Brinkman, Jacoline, additional, Buijs, Madelon, additional, Demir, Ayse, additional, Dijkstra, Ineke, additional, Endenburg, Silvia, additional, Engbers, Paula, additional, Gootjes, Jeannette, additional, Janssen, Marcel, additional, Kamphuis, Stephan, additional, Kniest-de, Jong Wilhelmina, additional, Kruit, Adrian, additional, Michielsen, Etienne, additional, Wolthuis, Albert, additional, van, Trotsenburg A.S. Paul, additional, den, Heijer Martin, additional, Bruinstroop, Eveline, additional, Boelen, Anita, additional, Heijboer, Annemieke C, additional, and den, Elzen Wendy, additional

Published
2024
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10. Assessing the HIV care continuum among transgender women during 11 years of follow‐up: results from the Netherlands' ATHENA observational cohort.

Author

Jongen, Vita W., Daans, Ceranza, van Sighem, Ard, Schim van der Loeff, Maarten, Hage, Kris, Welling, Camiel, von Vaupel‐Klein, Alex, den Heijer, Martin, Peters, Edgar J. G., van der Valk, Marc, Reiss, Peter, Prins, Maria, and Hoornenborg, Elske

Subjects
TRANS women, TRANSGENDER people, DELAYED diagnosis, CONTINUUM of care, CD4 lymphocyte count
Abstract

Introduction: Transgender women are at increased risk of acquiring HIV. Earlier studies reported lower retention in HIV care, antiretroviral therapy uptake, adherence and viral suppression. We assessed the stages of the HIV care continuum of transgender women in the Netherlands over an 11‐year period. In addition, we assessed new HIV diagnoses and late presentation, as well as disengagement from care, between 2011 and 2021. Methods: Using data from the Dutch national ATHENA cohort, we separately assessed viral suppression, as well as time to achieving viral suppression, among transgender women for each year between 2011 and 2021. We also assessed trends in new HIV diagnoses and late presentation (CD4 count of <350 cells/µl and/or AIDS at diagnosis), and disengagement from care. Results: Between 2011 and 2021, a total of 260 transgender women attended at least one HIV clinical visit. Across all years, <90% of transgender women were virally suppressed (207/239 [87%] in 2021). The number of new HIV diagnoses fluctuated for transgender women (ptrend = 0.053) and late presentation was common (ranging between 10% and 67% of new HIV diagnoses). Of the 260 transgender women, 26 (10%) disengaged from care between 2011 and 2021 (incidence rate = 1.10 per 100 person‐years, 95% confidence interval = 0.75−1.61). Conclusions: Between 2011 and 2021, less than 90% of transgender women linked to HIV care were virally suppressed. Late presentation at the time of diagnosis and disengagement from care were common. Efforts are needed to identify barriers to early HIV diagnosis and to optimize the different steps across the care continuum for transgender women. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Reflecting on the Importance of Family Building and Fertility Preservation: Transgender People's Experiences with Starting Gender-Affirming Treatment as an Adolescent.

Author

de Nie, Iris, Asseler, Joyce D., Arnoldussen, Marijn, Baas, Silke, de Vries, Annelou L.C., Huirne, Judith A.F., Steensma, Thomas D., den Heijer, Martin, and van Mello, Norah M.

Subjects
GENDER-nonconforming people, REPRODUCTIVE health, GENDER affirming care, INTERVIEWING, FAMILIES, REFLECTION (Philosophy), DECISION making, DESCRIPTIVE statistics, PARENTING, EXPERIENCE, SURVEYS, LONGITUDINAL method, HORMONE therapy, HUMAN reproduction, FERTILITY preservation, SEXUAL minorities, DATA analysis software
Abstract

Purpose: We aimed to investigate how adults, who started gender-affirming hormone treatment during adolescence, reflect on their reproductive decisions. Methods: We recruited transgender and gender-diverse (TGD) people who visited our gender identity clinic and commenced medical treatment in adolescence at least 9 years ago. We collected data through an online survey. Results: The cohort consisted of 89 participants (66 TGD people assigned female at birth (AFAB) and 23 TGD people assigned male at birth (AMAB) with a mean age of 32.4 years (range 25.5–51.2) at the time of study, and 15.6 years (range 11.5–20.6) at the start of medical treatment. All participants initiated medical treatment before 2014, when laws requiring sterilization for legal gender recognition were still in place, and only 30% of participants reported to have received information about fertility preservation, which none of them pursued. In addition, 96% of participants underwent gonadectomy and thus became permanently infertile, which was troublesome for 27%. With today's knowledge, 44% of TGD people AFAB and 35% of TGD people born AMAB would pursue fertility preservation. The percentage of participants with a (future) desire for children increased from 34% at the start of medical treatment (at adolescent age) to 56% at the time of this study (at adult age), of whom 23% had currently started a family. Conclusion: It is important to inform transgender adolescents about the effect of medical treatment on fertility and the options for fertility preservation since many may develop a desire for (biological) children when they reach adulthood. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

Author

Jiang, Xia, O’Reilly, Paul F, Aschard, Hugues, Hsu, Yi-Hsiang, Richards, J Brent, Dupuis, Josée, Ingelsson, Erik, Karasik, David, Pilz, Stefan, Berry, Diane, Kestenbaum, Bryan, Zheng, Jusheng, Luan, Jianan, Sofianopoulou, Eleni, Streeten, Elizabeth A, Albanes, Demetrius, Lutsey, Pamela L, Yao, Lu, Tang, Weihong, Econs, Michael J, Wallaschofski, Henri, Völzke, Henry, Zhou, Ang, Power, Chris, McCarthy, Mark I, Michos, Erin D, Boerwinkle, Eric, Weinstein, Stephanie J, Freedman, Neal D, Huang, Wen-Yi, Van Schoor, Natasja M, van der Velde, Nathalie, Groot, Lisette CPGM de, Enneman, Anke, Cupples, L Adrienne, Booth, Sarah L, Vasan, Ramachandran S, Liu, Ching-Ti, Zhou, Yanhua, Ripatti, Samuli, Ohlsson, Claes, Vandenput, Liesbeth, Lorentzon, Mattias, Eriksson, Johan G, Shea, M Kyla, Houston, Denise K, Kritchevsky, Stephen B, Liu, Yongmei, Lohman, Kurt K, Ferrucci, Luigi, Peacock, Munro, Gieger, Christian, Beekman, Marian, Slagboom, Eline, Deelen, Joris, Heemst, Diana van, Kleber, Marcus E, März, Winfried, de Boer, Ian H, Wood, Alexis C, Rotter, Jerome I, Rich, Stephen S, Robinson-Cohen, Cassianne, den Heijer, Martin, Jarvelin, Marjo-Riitta, Cavadino, Alana, Joshi, Peter K, Wilson, James F, Hayward, Caroline, Lind, Lars, Michaëlsson, Karl, Trompet, Stella, Zillikens, M Carola, Uitterlinden, Andre G, Rivadeneira, Fernando, Broer, Linda, Zgaga, Lina, Campbell, Harry, Theodoratou, Evropi, Farrington, Susan M, Timofeeva, Maria, Dunlop, Malcolm G, Valdes, Ana M, Tikkanen, Emmi, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Raitakari, Olli T, Mikkilä, Vera, Ikram, M Arfan, Sattar, Naveed, Jukema, J Wouter, Wareham, Nicholas J, Langenberg, Claudia, Forouhi, Nita G, Gundersen, Thomas E, Khaw, Kay-Tee, Butterworth, Adam S, Danesh, John, and Spector, Timothy

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Amidohydrolases, Autoimmune Diseases, Cohort Studies, Female, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Vesicular Transport Proteins, Vitamin D, White People
Abstract

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

Published
2018

14. A European Network for the Investigation of Gender Incongruence in adolescents

Author

Boogers, Lidewij S, primary, Wiepjes, Chantal M, additional, Staphorsius, Annemieke S, additional, Klink, Daniel T, additional, Ciancia, Silvia, additional, Romani, Alessia, additional, Stolk, Tessa H R, additional, van den Boogaard, Emmy, additional, Steensma, Thomas D, additional, de Vries, Annelou L C, additional, van Trotsenburg, A S Paul, additional, den Heijer, Martin, additional, Fisher, Alessandra D, additional, Cools, Martine, additional, and Hannema, Sabine E, additional

Published
2024
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21. Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis.

Author

Manousaki, Despoina, Dudding, Tom, Haworth, Simon, Hsu, Yi-Hsiang, Liu, Ching-Ti, Medina-Gómez, Carolina, Voortman, Trudy, van der Velde, Nathalie, Melhus, Håkan, Robinson-Cohen, Cassianne, Cousminer, Diana, Nethander, Maria, Vandenput, Liesbeth, Noordam, Raymond, Forgetta, Vincenzo, Greenwood, Celia, Biggs, Mary, Psaty, Bruce, Zemel, Babette, Mitchell, Jonathan, Taylor, Bruce, Lorentzon, Mattias, Karlsson, Magnus, Jaddoe, Vincent, Tiemeier, Henning, Campos-Obando, Natalia, Franco, Oscar, Utterlinden, Andre, Broer, Linda, van Schoor, Natasja, Ham, Annelies, Ikram, M, Karasik, David, de Mutsert, Renée, Rosendaal, Frits, den Heijer, Martin, Wang, Thomas, Lind, Lars, Orwoll, Eric, Mook-Kanamori, Dennis, Michaëlsson, Karl, Kestenbaum, Bryan, Ohlsson, Claes, Mellström, Dan, de Groot, Lisette, Grant, Struan, Kiel, Douglas, Zillikens, M, Rivadeneira, Fernando, Sawcer, Stephen, Timpson, Nicholas, Richards, J, and Rotter, Jerome

Subjects
GWAS, low-frequency genetic variants, multiple sclerosis, vitamin D, Cholestanetriol 26-Monooxygenase, Cytochrome P450 Family 2, Gene Frequency, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Multiple Sclerosis, Polymorphism, Single Nucleotide, Risk Factors, Vitamin D, Vitamin D Deficiency
Abstract

Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 × 10-88). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78-2.78, p = 1.26 × 10-12). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 × 10-5) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.

Published
2017

40. Exploring the role of low-frequency and rare exonic variants in alcohol and tobacco use

Author

Marees, Andries T., Hammerschlag, Anke R., Bastarache, Lisa, de Kluiver, Hilde, Vorspan, Florence, van den Brink, Wim, Smit, Dirk J., Denys, Damiaan, Gamazon, Eric R., Li-Gao, Ruifang, Breetvelt, Elemi J., de Groot, Mark C.H., Galesloot, Tessel E., Vermeulen, Sita H., Poppelaars, Jan L., Souverein, Patrick C., Keeman, Renske, de Mutsert, Renée, Noordam, Raymond, Rosendaal, Frits R., Stringa, Najada, Mook-Kanamori, Dennis O., Vaartjes, Ilonca, Kiemeney, Lambertus A., den Heijer, Martin, van Schoor, Natasja M., Klungel, Olaf H., Maitland-Van der Zee, Anke H., Schmidt, Marjanka K., Polderman, Tinca J.C., van der Leij, Andries R., Posthuma, Danielle, and Derks, Eske M.

Published
2018
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46. Continuation of gender-affirming hormones in transgender people starting puberty suppression in adolescence: a cohort study in the Netherlands

Author

van der Loos, Maria Anna Theodora Catharina, Hannema, Sabine Elisabeth, Klink, Daniel Tatting, den Heijer, Martin, Wiepjes, Chantal Maria, Pediatrics, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Reproduction & Development (AR&D), Internal medicine, APH - Aging & Later Life, and APH - Quality of Care

Subjects
Male, Adult, Adolescent, Puberty, Infant, Newborn, Gender Identity, Transgender Persons, Hormones, Cohort Studies, Pediatrics, Perinatology and Child Health, Developmental and Educational Psychology, Humans, Female, Netherlands
Abstract

Background: In the Netherlands, treatment with puberty suppression is available to transgender adolescents younger than age 18 years. When gender dysphoria persists testosterone or oestradiol can be added as gender-affirming hormones in young people who go on to transition. We investigated the proportion of people who continued gender-affirming hormone treatment at follow-up after having started puberty suppression and gender-affirming hormone treatment in adolescence. Methods: In this cohort study, we used data from the Amsterdam Cohort of Gender dysphoria (ACOG), which included people who visited the gender identity clinic of the Amsterdam UMC, location Vrije Universiteit Medisch Centrum, Netherlands, for gender dysphoria. People with disorders of sex development were not included in the ACOG. We included people who started medical treatment in adolescence with a gonadotropin-releasing hormone agonist (GnRHa) to suppress puberty before the age of 18 years and used GnRHa for a minimum duration of 3 months before addition of gender-affirming hormones. We linked this data to a nationwide prescription registry supplied by Statistics Netherlands (Centraal Bureau voor de Statistiek) to check for a prescription for gender-affirming hormones at follow-up. The main outcome of this study was a prescription for gender-affirming hormones at the end of data collection (Dec 31, 2018). Data were analysed using Cox regression to identify possible determinants associated with a higher risk of stopping gender-affirming hormone treatment. Findings: 720 people were included, of whom 220 (31%) were assigned male at birth and 500 (69%) were assigned female at birth. At the start of GnRHa treatment, the median age was 14·1 (IQR 13·0–16·3) years for people assigned male at birth and 16·0 (14·1–16·9) years for people assigned female at birth. Median age at end of data collection was 20·2 (17·9–24·8) years for people assigned male at birth and 19·2 (17·8–22·0) years for those assigned female at birth. 704 (98%) people who had started gender-affirming medical treatment in adolescence continued to use gender-affirming hormones at follow-up. Age at first visit, year of first visit, age and puberty stage at start of GnRHa treatment, age at start of gender-affirming hormone treatment, year of start of gender-affirming hormone treatment, and gonadectomy were not associated with discontinuing gender-affirming hormones. Interpretation: Most participants who started gender-affirming hormones in adolescence continued this treatment into adulthood. The continuation of treatment is reassuring considering the worries that people who started treatment in adolescence might discontinue gender-affirming treatment. Funding: None.

Published
2022

48. Effects of exogenous sex hormone use on sleep and depression: lessons learned from transgender users of gender-affirming hormones

Author

Morssinkhof, Margot W.L., primary, van den Ende, Daan, additional, van der Tuuk, Karin, additional, Wiepjes, Chantal, additional, Kreukels, Baudewijntje, additional, T'Sjoen, Guy, additional, van den Heuvel, Odile, additional, van der Werf, Ysbrand, additional, den Heijer, Martin, additional, and Broekman, Birit F.P., additional

Published
2023
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