Using the tools of genetic epidemiology to understand sex differences in neuropsychiatric disorders.
paper
Primary
Public
- Authors
- Merikangas, Alison K; Almasy, Laura
- Year
- 2020
- Journal
- Genes, brain, and behavior
- PMID
- 32348611
- DOI
- 10.1111/gbb.12660
- PMCID
- PMC7507200
Many neuropsychiatric disorders exhibit differences in prevalence, age of onset, symptoms or course of illness between males and females. For the most part, the origins of these differences are not well understood. In this article, we provide an overview of sex differences in psychiatric disorders including autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), anxiety, depression, alcohol and substance abuse, schizophrenia, eating disorders and risk of suicide. We discuss both genetic and nongenetic mechanisms that have been hypothesized to underlie these differences, including ascertainment bias, environmental stressors, X- or Y-linked risk loci, and differential liability thresholds in males and females. We then review the use of twin, family and genome-wide association approaches to study potential genetic mechanisms of sex differences and the extent to which these designs have been employed in studies of psychiatric disorders. We describe the utility of genetic epidemiologic study designs, including classical twin and family studies, large-scale studies of population registries, derived recurrence risks, and molecular genetic analyses of genome-wide variation that may enhance our understanding sex differences in neuropsychiatric disorders.
Male to female sex ratio of psychiatric disorders, sorted from most to least prevalent among females
The general multifactorial model of disease transmission. 65 The liability, or propensity for transmitting the disorder, is plotted on the X‐axis. The frequency distribution in the population is plotted on the Y‐axis. The shaded sections represent the proportion of affected individuals, light gray for males and dark gray for females. The multifactorial model specifies that numerous genetic and environmental factors is involved in an individual's liability for a particular disorder. The population mean (dash line) and threshold of liability after which the disorder becomes manifest is marked for males (dash dot line) and for females (long dash dot line). Sex differences in the liability to a condition may be tested by examining the risk to relatives of male versus female probands
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