Browsing by Subject "Sex differences"

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  • Torvik, Fartein Ask; Flato, Martin; McAdams, Tom A.; Colman, Ian; Silventoinen, Karri; Stoltenberg, Camilla (2021)
    Purpose: On average, boys have lower academic achievement than girls. We investigated whether the timing of puberty is associated with academic achievement, and whether later puberty among boys contributes to the sex difference in academic achievement. Method: Examination scores at age 16 were studied among 13,477 British twins participating in the population-based Twins Early Development Study. A pubertal development scale, a height based proxy of growth spurt, and age at menarche were used as indicators of puberty. Associations between puberty, sex, and academic achievement were estimated in phenotypic mediation models and biometric twin models. Results: Earlier puberty was associated with higher academic achievement both in boys and girls. The exception was early age at menarche in girls, which associated with lower academic achievement. More than half of the sex differences in academic achievement could be linked to sex differences in pubertal development, but part of this association appeared to be rooted in prepubertal differences. The biometric twin modelling indicated that the association between puberty and academic achievement was due to shared genetic risk factors. Genetic influences on pubertal development accounted for 7%-8% of the phenotypic variation in academic achievement. Conclusions: Pubertal maturation relates to the examination scores of boys and of girls. This can give genes related to pubertal maturation an influence on outcomes in education and beyond. Sex differences in pubertal maturation can explain parts of the sex difference in academic achievement. Grading students when they are immature may not accurately measure their academic potential. (c) 2021 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY license (
  • Wesolowska, Karolina; Elovainio, Marko; Koponen, Mikael; Tuiskula, Annukka M.; Hintsanen, Mirka; Keltikangas-Jarvinen, Liisa; Maattanen, Ilmari; Swan, Heikki; Hintsa, Taina (2017)
    We examined whether long QT syndrome (LQTS) mutation carrier status or symptomatic LQTS are associated with depression, and whether there are sex differences in these potential relationships. The sample comprised 782 participants (252 men). Of the 369 genetically defined LQTS mutation carriers, 169 were symptomatic and 200 were asymptomatic. The control group consisted of 413 unaffected relatives. Depression was assessed using the Beck Depression Inventory-II (BDI-II). No association was found for LQTS mutation carrier status with depression. The multinomial logistic regression showed that LQTS mutation carrier men with arrhythmic events scored higher on depression compared with the control group, even when adjusting for age, beta-blockers, antidepressants, and social support (OR = 1.09, 95 % CI [1.02, 1.15], p = .007). The binary logistic regression comparing symptomatic and asymptomatic LQTS mutation carriers showed that symptomatic LQTS was associated with depression in men (OR = 1.10, 95 % CI [1.03, 1.19], p = .009). The results were unchanged when additionally adjusted for education. These findings suggest that symptomatic LQTS is associated with depression in men but not in women. Overall, however, depression is more frequent in women than men. Thus, regular screening for depression in LQTS mutation carriers and their unaffected family members can be important.
  • Tabassum, Rubina; Ruotsalainen, Sanni; Ottensmann, Linda; Gerl, Mathias J.; Klose, Christian; Tukiainen, Taru; Pirinen, Matti; Simons, Kai; Widen, Elisabeth; Ripatti, Samuli (2022)
    Background Despite well-recognized differences in the atherosclerotic cardiovascular disease risk between men and women, sex differences in risk factors and sex-specific mechanisms in the pathophysiology of atherosclerotic cardiovascular disease remain poorly understood. Lipid metabolism plays a central role in the development of atherosclerotic cardiovascular disease. Understanding sex differences in lipids and their genetic determinants could provide mechanistic insights into sex differences in atherosclerotic cardiovascular disease and aid in precise risk assessment. Herein, we examined sex differences in plasma lipidome and heterogeneity in genetic influences on lipidome in men and women through sex-stratified genome-wide association analyses. Methods and Results We used data consisting of 179 lipid species measured by shotgun lipidomics in 7266 individuals from the Finnish GeneRISK cohort and sought for replication using independent data from 2045 participants. Significant sex differences in the levels of 141 lipid species were observed (P
  • Lee, Jamie; Prokopec, Stephenie D.; Watson, John D.; Sun, Ren X.; Pohjanvirta, Raimo; Boutros, Paul C. (2015)
    Background: 2,3,7,8-tetrachlorodibenzo-p-dixion (TCDD) is the most potent of the dioxin congeners, capable of causing a wide range of toxic effects across numerous animal models. Previous studies have demonstrated that males and females of the same species can display divergent sensitivity phenotypes to TCDD toxicities. Although it is now clear that most TCDD-induced toxic outcomes are mediated by the aryl hydrocarbon receptor (AHR), the mechanism of differential responses to TCDD exposure between sexes remains largely unknown. To investigate the differential sensitivities in male and female mice, we profiled the hepatic transcriptomic responses 4 days following exposure to various amounts of TCDD (125, 250, 500 or 1000 mu g/kg) in adult male and female C57BL/6Kuo mice. Results: Several key findings were revealed by our study. 1) Hepatic transcriptomes varied significantly between the sexes at all doses examined. 2) The liver transcriptome of males was more dysregulated by TCDD than that of females. 3) The alteration of " AHR-core" genes was consistent in magnitude, regardless of sex. 4) A subset of genes demonstrated sex-dependent TCDD-induced transcriptional changes, including Fmo3 and Nr1i3, which were significantly induced in livers of male mice only. In addition, a meta-analysis was performed to contrast transcriptomic profiles of various organisms and tissues following exposure to equitoxic doses of TCDD. Minimal overlap was observed in the differences between TCDD-sensitive or TCDD-resistant models. Conclusions: Sex-dependent sensitivities to TCDD exposure are associated with a set of sex-specific TCDD-responsive genes. In addition, complex interactions between the aryl hydrocarbon and sex hormone receptors may affect the observable differences in sensitivity phenotypes between the sexes. Further work is necessary to better understand the roles of those genes altered by TCDD in a sex-dependent manner, and their association with changes to sex hormones and receptors.
  • Nathan, K.; Lu, L. Y.; Lin, T.; Pajarinen, J.; Jämsen, E.; Huang, J-F; Romero-Lopez, M.; Maruyama, M.; Kohno, Y.; Yao, Z.; Goodman, S. B. (2019)
    Objectives Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage-mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male versus female cocultures. Methods A primary murine macrophage-MSC coculture system was used to demonstrate the optimal transition time from M1 to M2 (polarized from M1 with interleukin (IL)-4) macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase (ALP) activity, and osteocalcin protein secretion. Results We found that 96 hours of M1 phenotype in male cocultures allowed for maximum matrix mineralization versus 72 hours in female cocultures. ALP activity and osteocalcin secretion were also enhanced with the addition of IL-4 later in male versus female groups. The sex of the cells had a statistically significant effect on the optimal IL-4 addition time to maximize osteogenesis. Conclusion These results suggest that: 1) a 72- to 96-hour proinflammatory environment is critical for optimal matrix mineralization; and 2) there are immunological differences in this coculture environment due to sex. Optimizing immunomodulation during fracture healing may enhance and expedite the bone regeneration response. These findings provide insight into precise immunomodulation for enhanced bone healing that is sex-specific.
  • Hendriksen, L. C.; van der Linden, P. D.; Lagro-Janssen, A. L. M.; van den Bemt, P. M. L. A.; Siiskonen, S. J.; Teichert, M.; Kuiper, J. G.; Herings, R. M. C.; Stricker, B. H.; Visser, L. E. (2021)
    Background Adverse drug events, including adverse drug reactions (ADRs), are responsible for approximately 5% of unplanned hospital admissions: a major health concern. Women are 1.5-1.7 times more likely to develop ADRs. The main objective was to identify sex differences in the types and number of ADRs leading to hospital admission. Methods ADR-related hospital admissions between 2005 and 2017 were identified from the PHARMO Database Network using hospital discharge diagnoses. Patients aged >= 16 years with a drug possibly responsible for the ADR and dispensed within 3 months before admission were included. Age-adjusted odds ratios (OR) with 95% CIs for drug-ADR combinations for women versus men were calculated. Results A total of 18,469 ADR-related hospital admissions involving women (0.35% of all women admitted) and 14,678 admissions involving men (0.35% of all men admitted) were included. Most substantial differences were seen in ADRs due to anticoagulants and diuretics. Anticoagulants showed a lower risk of admission with persistent haematuria (ORadj 0.31; 95%CI 0.21, 0.45) haemoptysis (ORadj 0.47, 95%CI 0.30,0.74) and subdural haemorrhage (ORadj 0.61; 95%CI 0.42,0.88) in women than in men and a higher risk of rectal bleeding in women (ORadj 1.48; 95%CI 1.04,2.11). Also, there was a higher risk of admission in women using thiazide diuretics causing hypokalaemia (ORadj 3.03; 95%CI 1.58, 5.79) and hyponatraemia (ORadj 3.33, 95%CI 2.31, 4.81) than in men. Conclusions There are sex-related differences in the risk of hospital admission in specific drug-ADR combinations. The most substantial differences were due to anticoagulants and diuretics.
  • Prokopec, Stephenie D.; Watson, John D.; Lee, Jamie; Pohjanvirta, Raimo; Boutros, Paul C. (2015)
    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces myriad toxicities in most mammals. In rodents alone, there is a huge divergence in the toxicological response across species, as well as among different strains within a species. But there are also significant differences between males and females animals of a single strain. These differences are inconsistent across model systems: the severity of toxicity is greater in female rats than males, while male mice and guinea pigs are more sensitive than females. Because the specific events that underlie this difference remain unclear, we characterized the hepatic transcriptional response of adult male and female C57BL/6 mice to 500 mu g/kg TCDD at multiple time-points. The transcriptional profile diverged significantly between the sexes. Female mice demonstrated a large number of altered transcripts as early as 6 h following treatment, suggesting a large primary response. Conversely, male animals showed the greatest TCDD-mediated response 144 h following exposure, potentially implicating significant secondary responses. Nr1i3 was statistically significantly induced at all time-points in the sensitive male animals. This mRNA encodes the constitutive androstane receptor (CAR), a transcription factor involved in the regulation of xenobiotic metabolism, lipid metabolism, cell cycle and apoptosis. Surprisingly though, changes at the protein level (aside from the positive control, CYP1A1) were modest, with only FMO3 showing clear induction, and no genes with sex-differences. Thus, while male and female mice show transcriptional differences in their response to TCDD, their association with TCDD-induced toxicities remains unclear. (C) 2015 The Authors. Published by Elsevier Inc.
  • Lehtonen, Leevi (Helsingin yliopisto, 2021)
    Sex differences can be found in most human phenotypes, and they play an important role in human health and disease. Females and males have different sex chromosomes, which are known to cause sex differences, as are differences in the concentration of sex hormones such as testosterone, estradiol and progesterone. However, the role of the autosomes has remained more debated. The primary aim of this thesis is to assess the magnitude and relevance of human sex-specific genetic architecture in the autosomes. This is done by calculating sex-specific heritability estimates and genetic correlation estimates between females and males, as well as comparing these to sex differences on the phenotype level. Additionally, the heritability and genetic correlation estimates are compared between two populations, in order to assess the magnitude of sex differences compared to differences between populations. The analyses in this thesis are based on sex-stratified genome-wide association study (GWAS) data from 48 phenotypes in the UK Biobank (UKB), which contains genotype data from approximately 500 000 individuals as well as thousands of phenotype measurements. A replication of the analyses using three phenotypes was also made on data from the FinnGen project, with a dataset from approximately 175 000 individuals. The 48 phenotypes used in this study range from biomarkers such as serum testosterone and albumin levels to general traits such as height and blood pressure. The heritability and genetic correlation estimates were calculated using linkage disequilibrium score regression (LDSC). LDSC fits a linear regression model between test statistic values of GWAS variants and linkage disequilibrium (LD) scores calculated from a reference population. For most phenotypes, the heritability and genetic correlation results show little evidence of sex differences. Serum testosterone level and waist-to-hip ratio are exceptions to this, showing strong evidence of sex differences both on the genetic and the phenotype level. However, the overall correlation between phenotype level sex differences and sex differences in heritability or genetic correlation estimates is low. The replication in the FinnGen dataset for height, weight and body mass index (BMI), showed that for these traits the differences in heritability estimates and genetic correlations between the Finnish and UK populations are comparable or larger than the differences found between males and females.
  • Bonkhoff, Anna K.; Schirmer, Markus D.; Bretzner, Martin; Hong, Sungmin; Regenhardt, Robert W.; Donahue, Kathleen L.; Nardin, Marco J.; Dalca, Adrian; Giese, Anne-Katrin; Etherton, Mark R.; Hancock, Brandon L.; Mocking, Steven J. T.; McIntosh, Elissa C.; Attia, John; Cole, John W.; Donatti, Amanda; Griessenauer, Christoph J.; Heitsch, Laura; Holmegaard, Lukas; Jood, Katarina; Jimenez-Conde, Jordi; Kittner, Steven J.; Lemmens, Robin; Levi, Christopher R.; McDonough, Caitrin W.; Meschia, James F.; Phuah, Chia-Ling; Ropele, Stefan; Rosand, Jonathan; Roquer, Jaume; Rundek, Tatjana; Sacco, Ralph L.; Schmidt, Reinhold; Sharma, Pankaj; Slowik, Agnieszka; Sousa, Alessandro; Stanne, Tara M.; Strbian, Daniel; Tatlisumak, Turgut; Thijs, Vincent; Vagal, Achala; Wasselius, Johan; Woo, Daniel; Zand, Ramin; McArdle, Patrick F.; Worrall, Bradford B.; Jern, Christina; Lindgren, Arne G.; Maguire, Jane; Wu, Ona; Rost, Natalia S. (2023)
    This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and similar to 3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich dub regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.
  • Koponen, Marjaana; Bell, J. Simon; Lalic, Samanta; Watson, Rosie; Koivisto, Anne M.; Ilomäki, Jenni (2022)
    Background Guidelines highlight the importance of an individualized approach to treatment initiation for Parkinson's disease. Our aim was to investigate initiation of anti-Parkinson medication in Australia from 2013-2018, and to determine factors predicting choice of initial treatment. Methods Cohort of new-users (N = 4,887) of anti-Parkinson medication aged >= 40 years were identified from a 10% random representative sample of national medication dispensing data from July-2013 to June-2018. Changes in treatment initiation were examined across the whole cohort and stratified by age and sex. Results Treatment initiation was most frequent with levodopa followed by non-ergot dopamine agonists (DAs) and anticholinergics. Two thirds initiated with levodopa across the study period. Initiation with non-ergot DAs increased from 22 to 27% (rate ratio, RR 1.23, 95% confidence interval, CI 1.02-1.47) and initiation with anticholinergics decreased from 6.9% to 2.4% (RR 0.34, 95% CI 0.21-0.55) from 2013-2018. Among persons aged >= 65 years, one third of women and one fourth of men initiated on levodopa. Among women aged < 65 years, rates of treatment initiation with DAs (37%) and levodopa (37%) were similar in 2013/2014 but initiation with DA exceeded levodopa thereafter. Among men aged < 65 years, treatment initiation with levodopa (44%-49%) remained more frequent than initiation with DAs (29%-32%) throughout the study period. Conclusions Treatment initiation with levodopa was most frequent among persons aged >= 65 years, consistent with current guidelines. Whilst the value of levodopa sparing strategies is unclear, treatment initiation with DA has become increasingly common relative to levodopa among women but not among men aged < 65 years.
  • Lonnqvist, Jan Erik; Ilmarinen, Ville-Juhani (2021)
    We investigated the attitudes of the 11,410 candidates in the Finnish 2017 municipal elections who had responded to a Voting Advice Application. Women candidates were, both in terms of economic and social attitudes, more progressive than men. Building on the gender diagnosticity approach, we used responses to the attitude items to construct a dimensional measure of political genderedness; i.e., a measure of the femininity-masculinity of the individual's political attitudes. We used this measure to investigate the magnitude of sex differences across parties and the determinants of these differences. Sex differences were larger in parties with more economically right-oriented, socially conservative, well-off, and male candidates. Moreover, these differences were caused by men in these parties being different from other candidates. A similar methodology, in which a continuous measure of genderedness is used to assess sex differences, could be used in other domains of research on political behavior.
  • Lönnqvist, Jan-Erik; Leikas, Sointu; Verkasalo, Markku (2018)
    There is little research on how life transitions influence value priorities. Our purpose was to investigate, within the framework provided by Schwartz's Values Theory, the effects of entering parenthood on personal values. Study 1 (N = 12,850), employing cross-sectional European Social Survey data, showed that Finnish mothers, as compared to non-mothers, were closer to the Conservation pole of the value dimensions that opposes Conservation values with Openness to Change values. Study 2 longitudinally followed Finnish couples (N = 292) entering parenthood from the first weeks of pregnancy to three months after childbirth. Both self- and spouse-ratings of values showed that new mothers' value priorities shifted towards Conservation values. New mothers perceived a similar shift in new fathers' personal values, but no changes occurred in men's self-ratings. Neither study suggested change on the value dimension that opposes Self-Transcendence values with Self-Enhancement values. Across the cross-sectional and longitudinal designs, and across self- and spouse-ratings of values, our results consistently suggest that new mothers' shift their value priorities in the direction of increased Conservation over Openness to Change. These results are consistent with the notion that value change may facilitate adaptation to life events.
  • Chen, Li; Ling, Karen Tan Mei; Gong, Min; Chong, Mary F. F.; Tan, Kok Hian; Chong, Yap Seng; Meaney, Michael J.; Gluckman, Peter D.; Eriksson, Johan G.; Karnani, Neerja (2022)
    Background: Telomere length (TL) and its attrition are important indicators of physiological stress and biological aging and hence may vary among individuals of the same age. This variation is apparent even in newborns, suggesting potential effects of parental factors and the intrauterine environment on TL of the growing fetus. Methods: Average relative TLs of newborns (cord tissue, N = 950) and mothers (buffy coat collected at 26-28 weeks of gestation, N = 892) were measured in a birth cohort. This study provides a comprehensive analysis of the effects of heritable factors, socioeconomic status, and in utero exposures linked with maternal nutrition, cardiometabolic health, and mental well-being on the newborn TL. The association between maternal TL and antenatal maternal health was also studied. Results: Longer maternal TL (beta = 0.14, P = 1.99E-05) and higher paternal age (beta = 0.10, P = 3.73E-03) were positively associated with newborn TL. Genome-wide association studies on newborn and maternal TLs identified 6 genetic variants in a strong linkage disequilibrium on chromosome 3q26.2 (Tag SNP-LRRC34-rs10936600: P-meta = 5.95E-08). Mothers with higher anxiety scores, elevated fasting blood glucose, lower plasma insulin-like growth factor-binding protein 3 and vitamin B12 levels, and active smoking status during pregnancy showed a higher risk of giving birth to offspring with shorter TL. There were sex-related differences in the factors explaining newborn TL variation. Variation in female newborn TL was best explained by maternal TL, mental health, and plasma vitamin B12 levels, while that in male newborn TL was best explained by paternal age, maternal education, and metabolic health. Mother's TL was associated with her own metabolic health and nutrient status, which may have transgenerational effects on offspring TL. Conclusions: Our findings provide a comprehensive understanding of the heritable and environmental factors and their relative contributions to the initial setting of TL and programing of longevity in early life. This study provides valuable insights for preventing in utero telomere attrition by improving the antenatal health of mothers via targeting the modifiable factors.