Quality control and analytic best practices for testing genetic models of sex differences in large populations

Ekaterina A Khramtsova; Melissa A Wilson; Joanna Martin; Stacey J Winham; Karen Y He; Lea K Davis; Barbara E Stranger

doi:10.1016/j.cell.2023.04.014

Quality control and analytic best practices for testing genetic models of sex differences in large populations

Cell. 2023 May 11;186(10):2044-2061. doi: 10.1016/j.cell.2023.04.014.

Authors

Ekaterina A Khramtsova¹, Melissa A Wilson², Joanna Martin³, Stacey J Winham⁴, Karen Y He⁵, Lea K Davis⁶, Barbara E Stranger⁷

Affiliations

¹ Population Analytics and Insights, Data Science Analytics & Insights, Janssen R&D, Lower Gwynedd Township, PA, USA. Electronic address: ekhramts@its.jnj.com.
² School of Life Sciences, Center for Evolution and Medicine, Biodesign Center for Mechanisms of Evolution, Arizona State University, Tempe, AZ 85282, USA.
³ Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
⁴ Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA.
⁵ Population Analytics and Insights, Data Science Analytics & Insights, Janssen R&D, Lower Gwynedd Township, PA, USA.
⁶ Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
⁷ Center for Genetic Medicine, Department of Pharmacology, Northwestern University, Chicago, IL, USA. Electronic address: barbara.stranger@northwestern.edu.

PMID: 37172561
PMCID: PMC10266536 (available on 2024-05-11)
DOI: 10.1016/j.cell.2023.04.014

Abstract

Phenotypic sex-based differences exist for many complex traits. In other cases, phenotypes may be similar, but underlying biology may vary. Thus, sex-aware genetic analyses are becoming increasingly important for understanding the mechanisms driving these differences. To this end, we provide a guide outlining the current best practices for testing various models of sex-dependent genetic effects in complex traits and disease conditions, noting that this is an evolving field. Insights from sex-aware analyses will not only teach us about the biology of complex traits but also aid in achieving the goals of precision medicine and health equity for all.

Keywords: analytical methods; complex traits; genetic analyses; quality control; sex as a biological variable; sex chromosomes; sex differences.

Publication types

Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Female
Gene-Environment Interaction
Genome-Wide Association Study
Guidelines as Topic
Humans
Male
Models, Genetic*
Multifactorial Inheritance
Phenotype
Quality Control
Sex Characteristics*

Abstract

Publication types

MeSH terms

Grants and funding