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Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Background: Glioblastoma (GBM) patients are at particularly high risk for thrombotic complications. In the event of a postoperative pulmonary embolism, therapeutic anticoagulation (tAC) is indispensable. The impact of therapeutic anticoagulation on recurrence pattern in GBM is currently unknown. Methods: We conducted a matched-pair cohort analysis of 57 GBM patients with or without tAC that were matched for age, sex, gross total resection and MGMT methylation status in a ratio of 1:2. Patients’ characteristics and clinical course were evaluated using medical charts. MRI characteristics were evaluated by two independent authors blinded to the AC status. Results: The morphologic MRI appearance in first GBM recurrence showed a significantly higher presence of multifocal, midline crossing and sharp demarcated GBM recurrence patterns in patients with therapeutic tAC compared to the matched control group. Although statistically non-significant, the therapeutic tAC cohort showed increased survival. Conclusion: Therapeutic anticoagulation induced significant morphologic changes in GBM recurrences. The underlying pathophysiology is discussed in this article but remains to be further elucidated.