Keynote Lecture: Sexual dimorphism in polygenic risk

Value of the Information & Strength of the Argument

The lecture provides high-value synthesis of recent large-scale genomics studies, integrating multiple datasets and methodologies. The argumentation is coherent and evidence-based, with clear explanations of statistical models (linear mixed models, vQTLs, bivariate GWAS). Clark systematically evaluates the strength of evidence for sexual dimorphism, acknowledging limitations such as small effect sizes and the sensitivity of expression studies. He also introduces novel analytical approaches like variance QTLs and co-localization methods, strengthening the scientific contribution.

Scientific Rigor, Source Quality, Title Accuracy

The presentation is scientifically rigorous, citing multiple peer-reviewed papers and preprints from top groups (Bernabeu et al. bioRxiv; Rivas et al. in European Journal of Human Genetics; GTEx consortium analyses led by Stranger’s group). The speaker clearly distinguishes published results from his lab’s unpublished work. The title accurately represents the core theme: the prospects for using polygenic risk scores to reveal sex differences, which he evaluates critically. No comments were provided for analysis.

The title accurately reflects the content, focusing on the prospects and limitations of using polygenic risk scores to detect sexual dimorphism.

8/10

The presentation is based on peer-reviewed and preprint studies using large-scale datasets (UK Biobank, GTEx), with rigorous statistical methods. The speaker is a well-known population geneticist. Some claims are based on preprints, but overall the scientific quality is high.

Markers derived by PSI from the transcript: the creator did not define chapters.

• 00:30Introduction and acknowledgments; overview of lab's Drosophila research on sexual selection and sperm competition.
• 05:00Discussion of complex traits, linear mixed models, and the basis of GWAS.
• 12:00Introduction to UK Biobank and method of variance QTLs (vQTL) by Andrew Marderstein, including sex interaction with FTO locus and BMI.
• 25:00Review of published studies on SNP heritability concordance between sexes (Bernabeu et al., Flynn et al.) and sex-stratified GWAS yielding loci like waist-hip ratio and ankylosing spondylitis.
• 35:00Analysis of gene expression sex differences using GTEx: widespread tissue-specific differences, but very few sex-by-eQTL interactions; focus on X chromosome and epigenetic marks.
• 45:00Discussion of polygenic risk score transferability between sexes, particularly for hormone-responsive traits; concluding remarks on limits of detecting sexual dimorphism.

• Marderstein et al. (unpublished, in review) on variance QTLs — Cutting-edge method to identify SNPs influencing trait variance, applied to UK Biobank BMI data.
• Bernabeu et al. (bioRxiv, July 2020) on sex-stratified heritability — Study of 530 phenotypes from UK Biobank showing high concordance of SNP heritability between sexes.
• Flynn et al. (European Journal of Human Genetics, September 2020) on biomarkers — Analysis of 33 blood biomarkers showing similar heritabilities in males and females.
• Rivas et al. (Stanford) sex effect mixture model — Bivariate GWAS approach to identify sex-specific effects.
• Barbra Stranger's group study on GTEx (Nature Genetics?) — Comprehensive analysis of sex-biased gene expression across 44 tissues from 838 individuals.