Week 3- Genes and Heritability

Recap of Key Concepts

  • Categorical and dimensional approaches in understanding psychopathology.

  • Recognizes that risk factors may be transdiagnostic.

  • Emphasizes psychopathology as a developmental outcome.

    • Developmental cascades explored as interactions affecting future outcomes.

    • Developmental pathways include:

    • Continuity: maintaining stable characteristics over time.

    • Equifinality: multiple pathways leading to the same outcome.

    • Multifinality: same initial conditions leading to different outcomes.

  • Highlights how early development can predict psychopathology across the lifespan.

Genes and Heritability Overview

  • Course Information: PY0549

  • Instructor: Dr. Alyson Dodd

Lecture Structure

  • Focus areas include:

    • Behavioural genetics: the study of genetic influences on behavior.

    • Molecular genetics: exploration of the genetic makeup and its connection to psychological traits.

    • Parent psychopathology: examining how parents' mental health affects their offspring.

    • Gene x environment interactions: interplay between genetics and environmental factors in contributing to psychopathology.

Definitions

  • Offspring: Refers not only to individuals during childhood but also to grown-up children, encompassing the concept throughout psychopathology encompassing:

    • Genetic factors related to heritability.

    • Environmental risk factors influencing development.

Behavioural Genetics Revisited

  • Genotype: The genetic constitution of an individual, inherited genes.

  • Phenotype: Observable characteristics of an individual that may be influenced by genetic factors and environmental experiences.

Understanding Heritability

  • Heritability: The genetic contribution to variation in a trait or phenotype.

    • Ranges from 0-100%.

    • A heritability of 0.7 signifies that 70% of the variability in a trait within a population is attributable to genetic variation.

Typical Research Methods in Behavioural Genetics

  • Adoption and Family Studies: Analyzing psychopathology through:

    • Parent and offspring relationships.

    • Sibling and half-sibling comparisons.

  • Twin Studies: Examining the genetic similarities in:

    • Monozygotic (identical) twins: 100% shared genes.

    • Dizygotic (fraternal) twins: 50% shared genes.

Concordance Rates

  • Concordance: The frequency with which pairs (twins, siblings) share a trait.

    • Examples include color of eyes/hair, height, and various psychopathologies.

  • Differences noted between:

    • Monozygotic twins and Dizygotic twins.

    • Full siblings and half-siblings, generally showing higher concordance in MZ twins.

  • Assumes similar proportions of shared and unique environmental factors.

    • Growth context detailed by Whitney et al., (2025).

Disadvantages of Using Concordance in Studies

  • Note that concordance rates are not absolute; MZ twins may experience more similar environments.

  • Causation cannot be inferred merely from concordance rates.

  • Discrepancies in clinical versus population samples attributed to:

    • Measurement issues and diagnostic methodologies, often binary (present/absent).

    • Traits often exist on a dimensional scale.

    • Also referenced by Whitney et al., (2025).

Liability Threshold Models

  • Proposes that everyone holds some degree of liability (risk) for developing psychopathology.

    • Higher score reflects higher liability.

  • Diagnostic thresholds define the presence or absence of diagnosis, illustrating that risk exists along a continuum.

    • Specifically characterized by Whitney et al., (2025).

Evidence of Heritability

  • Analyzed through concordance rates and diagnostic thresholds.

  • Factors Considered:

    • Lower liability thresholds and broad phenotypes.

    • Emphasis on dimensional psychopathology derived from research involving twins and siblings (Allegrini et al., 2020; Hilker et al., 2018; Pettersson et al., 2018; Tick et al., 2015).

Changes Over Time in Heritability Evidence

  • Heritability estimates differ in studies and environments.

  • Highlights the role of environmental factors, which also vary: e.g., significant in broad phenotype analyses.

  • Longer follow-ups minimize data censoring issues (Allegrini et al., 2020; Hilker et al., 2018; Pettersson et al., 2018; Tick et al., 2015).

Implications of Heritability Findings

  • Greater concordance in MZ twins versus DZ twins supports genetic liability.

  • Highlights genetic influences in both categorical and dimensional approaches to psychopathology.

  • Acknowledgment that while psychopathology is heritable, the exact genes involved remain to be identified.

Assumptions in Molecular Genetics

  • Assumes specific disorders are associated with specific genes, being either monogenic or polygenic.

  • Genetics of psychopathology may vary by diagnosis.

  • Emphasizes a biological basis for genetic influence on disorder, largely independent of environmental factors.

Genetic Causes of Psychopathology

  • Variability in genetic mutations:

    • Chromosomal abnormalities observed in conditions like Phenylketonuria, Down’s syndrome, Fragile X, and Williams syndrome.

Psychopathology with Established Genetic Causes

  • Confirmed through genetic testing, capturing both inherited and de novo mutations.

  • Notes that not all aspects of a phenotype directly relate to genetic factors; deviations have cascading effects throughout development (Whitney et al., 2025).

Genetic Variants in Research

  • Variants identified:

    • Copy Number Variants (CNVs)

    • Single Nucleotide Polymorphisms (SNPs)

  • Ranges from common variants with smaller effects to rarer variants with larger effects (Smoller et al., 2019; Whitney et al., 2025).

Genome-Wide Association Studies (GWAS)

  • Involves scanning genomes for genetic variants, especially common SNPs.

  • Investigate whether these variants correlate with traits across large populations, categorized as cases versus controls.

  • The methodology requires substantial sample sizes (Smoller et al., 2019; Whitney et al., 2025).

Findings from Genome-Wide Association Studies

  • SNPs that achieve genome-wide significance linked to various psychopathologies, including dimensional psychopathology.

  • Identifies that genetic influences are polygenic and typically exhibit small effect sizes, lower than twin/family study estimates, indicating the role of environmental influences.

  • Supported by findings from the Cross-Disorder Consortium of the Psychiatric Genomics Consortium (2013), Jami et al. (2022).

Cross-Disorder Associations

  • Researching shared genetic vulnerabilities among disorders helps to determine if genetic variants overlap across different psychopathologies.

  • Evaluates whether these associations extend beyond distinct diagnoses to generalize across diagnoses and dimensions (Cross-Disorder Consortium of the Psychiatric Genomics Consortium, 2013; Jami et al., 2022).

Polygenic Risk Scores (PRS)

  • Derived from GWA studies to identify multiple genetic variants contributing to a trait (e.g., psychopathology).

  • Reflects the idea that multiple genes contribute cumulatively to risk;

    • Higher scores correlate with greater risk across populations.

Specificity in Polygenic Risk Scores for Adult Psychopathology

  • PRS linked to adult diagnoses as indicators for earlier psychosocial phenotypes.

  • Emphasizes consistent genetics across various psychopathological traits.

  • Observations indicate that PRS may illustrate not only generalized liability but domain-specific risks the change over time, highlighting increasing specificity (Allegrini et al., 2020; Neumann et al., 2021; Riglin et al., 2020).

Molecular Genetics in Psychopathology: Current State

  • Molecular genetics in psychopathology remain complex and largely polygenic.

  • Common genetic variants like SNPs yield numerous contributors though rarer variants typically show greater effects.

  • The field is moving towards analyses that consider cross-disorder implications, emphasizing complex connections and pleiotropy—indicating genes operating beyond DSM classifications (Andreason et al., 2023; Smoller et al., 2019; Whitney et al., 2025).

Molecular Genetics and Heritability Estimates

  • Clarifies that SNP heritability is typically lower than estimates derived from twin studies due to the missing heritability problem.

Missing Heritability Problem

  • Examines discrepancies in methodologies resulting in potential overestimations of heritability.

  • Considers whether smaller molecular effects or rare genetic variants have gone unnoticed due to variability in identification practices (Andreason et al., 2023; Joseph, 2012).

Parent Psychopathology

  • Investigates the timing and nature of parental exposure to psychopathology across developmental stages:

    • In utero influences biological pathways impacting fetal development.

    • During childhood, behavioral modeling correlates with parental mental health.

  • Highlights intergenerational transmission as being influenced by genetic and environmental factors, stressing it is not predetermined (Aktar et al., 2019; Bailey et al., 2021).

Evidence Linking Parental and Offspring Psychopathology

  • Maternal and paternal mental health conditions correlate with child psychopathology, with evolving risk factors over time and stability in lower levels reducing risks.

  • Suggests a bidirectional relationship where outcomes can influence parental mental health (Bailey et al., 2021; Xerxa et al., 2020).

Gene x Environment Interactions

  • Emergent evidence focusing on Diathesis-stress models suggests interactions leading to psychopathology.

  • Highlighting adversity as a focus, including parental mental health's effects.

  • Findings remain mixed with complex interrelations recognized among diverse individual experiences (Musci et al., 2019).

Summary of Key Findings

  • The interplay between genetic and environmental factors brings to light the reality that heritability estimates are not absolute; genetic contributions do exist but limited.

  • Acknowledges the predictive nature of parent psychopathology on offspring risk and necessitates attention to misconduct of assumptions toward genetic determinism, advocating for environmental interactions.

Core and Recommended Readings

  • Core Reading:

    • Bailey et al. (2021), Neumann et al. (2022) focus on connections between maternal distress and adolescent psychopathology.

  • Recommended Reading:

    • Hilker et al. (2018), Mistry et al. (2018) examining heritability within specific disorders.

  • Further Reading:

    • Reviews on genetic influences on various psychiatric disorders and their implications and multidimensional approaches.

References

  • Comprehensive citations exploring genetic influences on psychopathology, including works by notable authors in the field such as Allegrini et al. (2020), Aktar et al. (2019), and Jami et al. (2022), with a focus on major scientific discussions surrounding genetic links and environmental factors that affect development across the lifespan.