Askelund, A. D. | Search bioRxiv

bioRxiv2026

Sex differences in the genetic basis of human recombination within 190,000 parent-child pairs

Structured AbstractO_ST_ABSIntroductionC_ST_ABSSexual reproduction uses a specialized cell division called meiosis, in which a single round of DNA replication is followed by two cell divisions to create hap-loid gametes. Genetic recombination in meiosis assures faithful segregation of chromosomes and establishes patterns of genetic linkage and inheritance. Meiotic recombination is thus a fundamental genomic process that shapes major features of the genomic landscape, influences mutation, and creates genetic diversity. RationaleThe genetic basis of between-individual variation in the occurrence and genomic location of meiotic recombination events remains poorly understood in humans. In particular, we lack an understanding of whether the same DNA regions shape vari-ation in recombination rates across studies. We address this by curating 112,144 maternal and 78,653 paternal meiosis events (parent-child pairs) across cohorts from four countries, creating the largest dataset of its kind. ResultsWe identify 58 independent genomic regions associated with the occurrence and genomic location of recombination events, 24 of which are unique across phe-notypes. Of the 24 unique regions, 6 are novel and specific to female meiotic recombination harboring genes linked to ovarian function, a 7th novel region is linked to male recombination. Many regions have significant sex-dependent ef-fects across studies. We estimate the between-sex genetic correlation for meiotic recombination rate to be 0.374 (0.072 SD), which captures the extent to which the genetic factors influencing a trait in one sex also impact the same trait in the other. 30-40% of the individual-level variation in recombination rate is at-tributable to DNA markers, of which only 37.7% (2.7% SD) and 47.1% (3.8% SD) is attributable to previously known global modulators of meiotic recombi-nation, in females and males respectively. We create a polygenic predictor that significantly predicts recombination rates of both women and men after adjusting for age and year of birth. We find significant correlations between female meiotic recombination, reproductive outcomes and reproductive aging, after adjusting for study ascertainment. ConclusionsIn the largest meta-analysis to date of human meiotic recombination, we identify novel loci with sex-specific effects that influence male and female recombination rate across multiple cohorts.

genomics↗

bioRxiv2018

Positive memory specificity reduces adolescent vulnerability to depression

Depression is the leading cause of ill health and disability worldwide1. A known risk factor of depression is exposure to early life stress2. Such early stress exposure has been proposed to sensitise the maturing psychophysiological stress system to later life stress3. Activating positive memories dampens acute stress responses with resultant lower cortisol response and improved mood in humans4 and reduced depression-like behaviour in mice5. It is unknown whether recalling positive memories similarly reduces adolescent vulnerability to depression. Here we used path modelling to examine the effects of positive autobiographical memory specificity on later morning cortisol and negative self-cognitions during low mood in adolescents at risk for depression due to early life stress (n = 427, age: 14 years)6. We found that experimentally assessed positive but not negative memory specificity was associated with lower morning cortisol and less negative self-cognitions during low mood one year later. Moderated mediation analyses demonstrated that positive memory specificity reduced later depressive symptoms through lowering negative self-cognitions in response to negative life events reported in the one-year interval. Positive memory specificity actively dampened the negative effect of stressors over time, thereby operating as a resilience factor reducing the risk of subsequent depression7. These findings suggest that developing methods to improve positive memory specificity in at-risk adolescents may counteract vulnerability to depression.

neuroscience↗