Capturing Gender Diversity in Twin Research.Twin research and human genetics : the official journal of the International Society for Twin Studies • April 15, 2025
Will Conabere, Anja Ravine, Louise Bourchier, Sue Malta, Jessica Tyler, Shuai Li, John Hopper, Ken Pang
Most twin registries have not systematically collected the data required to determine gender identity, which has limited opportunities to evaluate potential familial contributors to gender diversity. This study addresses this gap by analyzing responses to gender identity questions introduced in Twins Research Australia's 2023 survey. Among 4475 respondents (mean age 52.2 years, SD = 15.3), 36 (0.8%) indicated a transgender or gender diverse identity, which is consistent with population-based estimates of gender diversity internationally. Gender diversity co-occurred in 2/19 monozygotic pairs and 0/8 dizygotic pairs, giving rise to tetrachoric correlations of 0.62 (95% CI [0.33, 0.87]) and 0.00 (95% CI [0.00, 0.88]), respectively. These results broadly align with previous concordance estimates from twin studies that were specifically focused on gender identity. Although limited by a small sample size, these findings demonstrate the feasibility and utility of systematically collecting gender identity data through routine twin registry surveys.
Adverse late outcomes in long-term survivors of young adult Hodgkin lymphoma (YAHL) compared to their unaffected co-twins.Leukemia & lymphoma • May 01, 2025
Marcie Haydon, Amie Hwang, Niquelle Wadé, Jun Wang, Jia Wan, Marta Epeldegui, Yu Guo, Laura Buchanan, Esther Lam, Larry Magpantay, Shuai Li, Lucas Calais Ferreira, Joel Milam, Otoniel Martinez Maza, Thomas Mack, John Hopper, David Conti, Wendy Cozen
Late-onset conditions have been reported in young adult Hodgkin lymphoma (YAHL) survivors but the use of convenience controls may bias estimates. Thirty-five YAHL survivors and their unaffected co-twins completed an online questionnaire on such conditions. McNemar's test and conditional logistic and random-effects linear regression were used to assess differences. On average, YAHL survivors (54.3% monozygotic, 57.1% female) were 27.1 years at diagnosis and 29.7 years post-diagnosis at participation. Survivors had increased risk of secondary malignancy (OR = 4.33), cardiac (12 cases/0 co-twins), lung (6 cases/0 co-twins), and thyroid conditions (18 cases/0 co-twins), and increased utilization of cardiac (OR = 9.00) and thyroid tests (OR = 10.00) compared to their co-twin. Non-significant trends in life milestone achievement, including greater college degree attainment, earlier retirement, and fewer biological children, were also observed in YAHL survivors. Life satisfaction was significantly lower among YAHL survivors (p = .035). Decades after diagnosis, differences in late outcomes were observed in YAHL survivors compared to co-twin controls, providing a more accurate assessment of the late effects of YAHL.
Opposing effects between retinoic acid and Fibroblast growth factor in patterning the common crus and semicircular canals of the inner ear.Developmental biology • February 25, 2025
Weise Chang, John Hopper, Doris Wu
The three orthogonally arranged semicircular canals and their sensory organs, cristae, of the inner ear are responsible for detecting angular head movements. A main functional component of this vestibular apparatus is the evolutionarily conserved unit of the anterior and posterior canals joined by a central stalk, the common crus. A resorption process (removal of epithelial cells) carves out these three connecting structures from an epithelial outpocket of the developing otic vesicle known as the vertical canal pouch. While molecules such as Fibroblast growth factors (FGF) and Bone morphogenetic proteins (BMP) emanating from the prospective sensory cristae and the rim of the canal pouch, counteract with the resorption process to form the canals, it is not known if there is an independent mechanism that mediates common crus formation. Here, we show that genes encoding retinoic acid (RA) synthesizing enzymes, Aldh1a2 and Aldh1a3, are expressed in the presumptive common crus region of the canal pouch. Blocking endogenous RA activity abolishes common crus formation. Endogenous RA may mediate common crus formation by limiting proliferation of the peri-otic mesenchyme at the prospective common crus region and thus counteracting the resorption process. Additionally, RA and FGF antagonize each other in patterning the common crus and canals, respectively. Ectopic FGF2 downregulates Aldh1a2 expression in the common crus, whereas Bmp2, required for canal formation, may be an intermediate which is co-regulated by RA and FGF.
Allergic disease and risk of multiple myeloma: A case-control study.Cancer epidemiology • December 22, 2024
Simon Cheah, Adrian Lowe, Nina Afshar, Julie Bassett, Fiona Bruinsma, Wendy Cozen, Simon Harrison, John Hopper, Harindra Jayasekara, H Prince, Claire Vajdic, Nicole Doo, Graham Giles, Shyamali Dharmage, Roger Milne
Objective: Multiple myeloma (MM) is responsible for significant morbidity and mortality, yet our knowledge regarding MM aetiology remains limited. We investigated whether a history of allergic conditions is associated with MM risk.
Methods: Incident cases (n = 782) of MM were recruited via cancer registries in Victoria and NSW. Controls (n = 733) were siblings (n = 436) or spouses (n = 297) of cases. Unconditional logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for associations between self-reported allergic conditions (asthma, eczema, food allergy, hay fever) and MM risk.
Results: Eczema was inversely associated with MM risk (OR = 0.54, 95 %CI = 0.42-0.70), as was a combined history of food allergy and eczema (OR = 0.52, 95 %CI = 0.29-0.93). There was an inverse association between a history of any allergic condition (compared with none) and risk of MM (OR = 0.68, 95 %CI = 0.55-0.84). In the mean-centred dose-risk analysis the OR was 0.87 (95 %CI = 0.73-1.04) per additional allergic condition of interest. No notable associations were identified for food allergy, asthma, or hay fever alone.
Conclusions: We found that a history of allergic disease, particularly eczema, was associated with reduced MM risk. Further research is recommended to confirm findings and investigate potential mechanisms.
Cancer incidence inconsistency between UK Biobank participants and the population: a prospective cohort study.BMC Medicine • December 09, 2024
Chenxi Li, Gillian Dite, Tuong Nguyen, John Hopper, Shuai Li
Background: While the UK Biobank has been widely used for cancer research, its representativeness of the population in terms of cancer incidence has not been thoroughly investigated.
Methods: We conducted a prospective cohort study of 466,163 UK Biobank participants who were cancer-free at recruitment. Standardised incidence ratios (SIRs) were calculated for all cancers combined and for 25 cancers, by comparing incidences for the participants with the UK national incidences. Variations in SIR by age, sex and deprivation measures were investigated.
Results: Over a median follow-up period of 12 years, 47,535 participants had a cancer diagnosis. The SIR for all cancers combined was 0.90 (95% CI: 0.89, 0.91). The SIR increased with age and deprivation (P = 10-9). The SIRs of 17 cancers differed from 1 (Bonferroni-adjusted P < 0.05): for prostate cancer and melanoma the SIRs were 1.2 and for the other 15 cancers the SIRs ranged from 0.43 to 0.93. The SIRs of 13 cancers differed by deprivation: the greater the deprivation, the lower the SIRs for prostate cancer and melanoma, and the higher the SIRs for the other 11 cancers.
Conclusions: The overall cancer incidence was 10% lower for the UK Biobank participants compared with the population, with most cancers having a lower incidence that increased with deprivation. Irrespective of their causes, the inconsistencies could bias UK Biobank research results related to absolute cancer risks, such as the development and/or validation of cancer risk models and penetrance estimates for cancer susceptibility genes.
