FAQs on Human Genomics Studies

FAQs on Human Genomics Studies

Genomic Findings on Human Behavior and Social Outcomes: FAQs

CONTENTS

About this work: Many genetic scientists have taken steps to pre-emptively avoid misconceptions and misapplications of their work by creating frequently asked questions (FAQs) to explain their findings in specific studies. These FAQs give the context, scope, and limitations of their research. More on this project.

A note on limitations: Each FAQ linked below includes special attention to important scope, limitations, and misconceptions regarding results of genomic studies. Many of these limitations are shared by all studies. Given that part of the goal of this FAQ repository is to increase access to information that may help mitigate misunderstanding or misuses of results, here we’d like to briefly emphasize a few key limitations of the studies linked below:

  • Genetic influences on behavioral traits are not immutable or deterministic.
  • The mechanisms through which genetic variants are associated with social and behavioral outcomes is poorly understood and are not divorced from environmental or social processes.
  • Genetic variants identified by GWAS have miniscule effects, typically ranging from .01-.03%.
  • PGS for complex behavioral traits are not currently useful predictors of individual outcomes–i.e., polygenic scores are not “fortune-tellers.”
  • The results of genomic studies listed here do not provide the genetic bases of ancestral, racial, or ethnic differences in human behavior.
  • Genetic ancestry is not synonymous with the socially defined concept of race.
  • Almost all genomic studies listed here were conducted in populations of European descent and cannot be meaningfully extrapolated to other populations.

These limitations apply to the majority of FAQs included in this repository. For other limitations to GWAS and PGS see: “Genomics, Behavior, and Social Outcomes” in The Hastings Center’s Bioethics Briefings.

Also see: “Wrestling with Social and Behavioral Genomics: Risks, Potential Benefits, and Ethical Responsibility,” a project of The Hastings Center and Geisinger, with Columbia University and Stanford University.

Genomic Studies of Educational Traits & Outcomes

GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment

What did the study examine? Known as “EA1,” this was the first large-scale genomic study of educational attainment. Link to the study.
What year was it published? 2013
Key findings:
1. The study identified three common genetic variants (called single-nucleotide polymorphisms, or SNPs) that were significantly associated with EA.
2. The study’s polygenic score for EA explained a little over 2% of the total variation of EA in the population studied.
Corresponding author of FAQ: Dan Benjamin (daniel.benjamin@gmail.com)
Additional link: thessgac.org

Genome-wide Association Study Identifies 74 Loci Associated with Educational Attainment

What did the study examine? Known as “EA2,” it was the second large-scale study that examined the relationship between variation in the human genome and educational attainment (EA),  the number of years of school a person completes. Link to study.
What year was it published? 2016
Key findings:
1. Researchers identified 74 genetic variants associated with the number of years of school a person has completed.
2. Collectively, these variants explained a fraction of a percent of the variation in educational attainment across individuals in the sample. However, the polygenic score created using this sample was higher than the 2013 study by Benjamin et al (FAQ below) and explained 3.2% of the total variation across individuals.
Corresponding author of FAQ: Dan Benjamin (daniel.benjamin@gmail.com)
Additional link: thessgac.org

Gene Discovery and Polygenic Prediction from a 1.1-Million-Person GWAS of Educational Attainment

What did the study examine? Known as “EA3,” this is the largest and most well-known genomic investigation of educational attainment. Link to the study.
What year was it published? 2018
Key findings:
1. The study found 1,271 genetic variants associated with EA.
2. Polygenic scores explain 11% – 13% of the total variance in educational attainment and 7% -10% of the variance in cognitive performance
Corresponding author of FAQ: Dan Benjamin (daniel.benjamin@gmail.com)
Additional link: thessgac.org

Common Genetic Variants Associated with Cognitive Performance Identified Using Proxy-Phenotype Method

What did the study examine? This study examined the relationship between the genome and cognitive performance, defined by the authors as performance by healthy individuals on cognitive tests such as IQ scales. Link to the study.
What year was it published? 2014
Key findings:
1. The study found three genetic variants with a statistically significant association with cognitive performance.
2. The effect of these variants was extremely small, with each variant accounting for approximately 0.3 points on a standard IQ scale (which has a mean of 100 and standard deviation of 15).
3. A polygenic score derived from 60 of the education-associated genetic variants were also found to be associated with memory and absence of dementia.
Corresponding author of FAQ: Dan Benjamin (daniel.benjamin@gmail.com)
Additional link: thessgac.org

Genetic Associations with Mathematics Tracking and Persistence

What did the study examine? This study examined the relationship between individuals’ genetics and progress in high school mathematics courses as shown by difficulty of the math courses they took and persistence in studying math.  Link to the study.
What year was it published? 2020
Key findings:
1. On average, students with more education-related genetic variants took more advanced math classes in the 9th grade.
2. On average, students with more education-related genetic variants stayed in math for longer.
3. Students with fewer education-related genetic variants were less likely to drop out of math if they attended a school where most parents had graduated from high school, demonstrating the importance of social and environmental factors.
Corresponding author of FAQ: K. Paige Harden (harden@utexas.edu)

The Earliest Origins of Genetic Nurture: The Prenatal Environment Mediates the Association between Maternal Genetics and Child Development

What did the study examine? This study examined the relationship between parent’s genetics and children’s academic development and performance. Link to the study.
What year was it published? 2020
Key findings:
1. Mothers with a greater number of education-related genetic variants (identified through previous GWAS of educational attainment) were generally healthier and more financially stable during pregnancy.
2. Mothers’ experiences during pregnancy (e.g., social and economic resources, physical and mental health) explained up to one-third of the associations between maternal genes and children’s developmental and academic outcomes at ages 4 to 7 years.
Corresponding authors of FAQ: Emma-Armstrong Carter (emmaac@stanford.edu) and Sam Trejo (samtrejo@stanford.edu)

Genomic Studies of Social and Environmental Factors

Molecular Genetic Contributions to Social Deprivation and Household Income in UK Biobank

What did the study examine? This study examined the relationship between genomic variation, and social deprivation and household income. Link to the study.
What year was it published? 2016
Key findings:
1. The reasons that people differ in social deprivation and income are mostly environmental. There is a small genetic contribution to these factors.
2. Researchers found that variation across the 17 million genetic variants studied explained 21% of the variation in social deprivation and 11% of the variation in household income between individuals in the sample.
3. Four genetic variants were statistically significantly associated with household income, no genetic variants were significantly associated with social deprivation.
4. Many of the genetic variants discovered in this study were also shown to exist in regions of the genome that are associated with intellectual disabilities and schizophrenia.
Corresponding author of FAQ: David Hill (David.Hill@ed.ac.uk)

Genetic Correlates of Social Stratification in Great Britain

What did the study examine? This study investigated the extent to which behaviors and outcomes like physical health, mental health, personality, height, educational attainment, BMI, substance use, and reproduction demonstrated regional differences in DNA. Link to the study.
What year was it published? 2019
Key findings:
Genetic variants associated with educational attainment exhibited the strongest clustering. For example, researchers found that genetic variants associated with lower educational attainment were more common in geographic areas that faced economic challenges. In comparison, genetic variants associated with higher educational attainment were more common in richer areas and among children whose parents have greater levels of education and subsequently the resources to provide a better learning environment.
Corresponding author of FAQ: Abdel Abdellaoui (a.abdellaoui@amsterdamumc.nl)
Related links:
https://www.the-scientist.com/news-opinion/opinion–the-nature-of-social-inequalities-in-great-britain-66607
https://www.nature.com/articles/d41586-019-03171-6

Genome-wide analysis identifies molecular systems and 149 genetic loci associated with income (Supplementary Note 2)

What did the study examine? This study examined the relationship between genomic variation and household income in the UK. Link to the study.
What year was it published? 2019
Key findings:
1. Genetic variation was associated with 7% of variation in household income.
2. 149 independent genetic variants were statistically significantly associated with household income.
3. The genetic differences linked to higher income were also linked to a longer life, better physical health, and better well-being.
4. Some evidence was found that suggests intelligence may be causally related to income in the U.K.
Corresponding author of FAQ: David Hill (David.Hill@ed.ac.uk)

Genomic Studies of Psychological and Psychiatric Behaviors

Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction

What did the study examine? This study examined the relationship between genomic variation and noncognitive behavioral traits related to success in school, such as motivation, persistence, grit, curiosity, self-control, and growth mindset. Link to the study.
What year was it published? 2020
Key findings:
1. The study identified 157 genetic variants associated with non-cognitive skills.
2. These genetic variants were also correlated with genetic variants associated with socioeconomic status (SES) and longevity.
3. Genetic variants associated with non-cognitive skills were also associated with personality, decision-making, risk-behavior, and increased risk for psychiatric disorders.
Corresponding author of FAQ: K. Paige Harden (harden@utexas.edu)

Genetic Variants Associated with Subjective Well-Being, Depressive Symptoms and Neuroticism Identified through Genome-Wide Analyses

What did the study examine? This study examined the relationship between genetics and subjective well-being, depressive symptoms, and neuroticism. Link to the study.
What year was it published? 2016
Key findings:
1. Three genetic variants were associated with subjective well-being.
2. Two genetic variants were associated with depressive symptoms.
3. Eleven genetic variants were associated with neuroticism.
4. The estimated effect of these variants was small. For instance, each of the genetic variants associated with depressive symptoms and neuroticism account for only 0.02% to 0.04% of the variation of these outcomes in the population studied.
Corresponding author of FAQ: Dan Benjamin (daniel.benjamin@gmail.com)

What did the study examine? This study examined the relationship between genetics, and behaviors and disorders related to impulse-control and self-regulation, i.e., externalizing behavior. Link to the study.
What year was it published? 2020 (preprint)
Key findings:
1. The study identified 579 genetic variants associated with externalizing behavior or impulse-related variables, including attention-deficit/hyperactivity disorder, problematic alcohol use, lifetime cannabis use, age at first sexual intercourse, number of sexual partners, general risk tolerance, and lifetime smoking initiation.
2. This study’s polygenic score captures up to 10% of the variance in externalizing behaviors, but less than that for any specific behavior or outcome (e.g., ADHD).
3. The genetic variants identified in this study were also associated with a wide range of additional behavioral and medical outcomes, such as opioid use disorder, suicide, HIV infections, unemployment, and criminal convictions.
Corresponding author of FAQ: K. Paige Harden (harden@utexas.edu)

Childhood Trauma, Life-Time Self-Harm, and Suicidal Behaviour and Ideation Are Associated with Polygenic Scores for Autism

What did the study examine? This study examined whether genetic variants associated with autism are also associated with childhood trauma. Link to the study.
What year was it published? 2019
Key findings:
1. Individuals with a greater number of autism-associated genetic variants were more likely to report childhood trauma, self-harm, and suicidal ideation.
2. Several social and environmental factors influenced the relationship between autism-associated genetic variants and trauma.
3. It is important to identify sources of trauma for autistic individuals in order to reduce their occurrence and impact.
4. The associations were very small for all outcomes.
Corresponding author of FAQ: Varun Warrier (vw260@medschl.cam.ac.uk)

Genome-Wide Association Analyses of Risk Tolerance and Risky Behaviors in over 1 Million Individuals Identify Hundreds of Loci and Shared Genetic Influences

What did the study examine? This study examined the relationship between genetics on the one hand and risk tolerance as well as risky behaviors related to driving, drinking, smoking, and sexual behavior, on the other. Link to the study.
What year was it published? 2019
Key findings:
1. The study identified 124 genetic variants associated with a person’s willingness to take risks.
2. The study also found evidence of shared genetic influences across both an overall measure of risk tolerance and many specific risky behaviors, including speeding, drinking, tobacco and cannabis consumption, riskier investments, and sexual behavior.
Corresponding author of FAQ: Jonathan Beauchamp (jonathan.pierre.beauchamp@gmail.com)

Genomic Studies of Sexual Behaviors

Genome-wide Analysis Identifies 12 Loci Influencing Human Reproductive Behavior

What did the study examine? Researchers sought to identify genetic variants that are related to a person’s age at the birth of their first child and number of children ever born, and to examine their biological function. Link to study
What year was it published? 2018
Key findings:
1. The study identified 12 genetic variants statistically significantly associated with human reproductive behavior, each with small effect sizes.
2. The study’s polygenic score predicts around 0.2% of the variability of the number of children an individual will have in the course of their lifetime.
Corresponding author of FAQ: Melinda Mills (melinda.mills@nuffield.ox.ac.uk

Perspectives on the Complex Genetics of Same-Sex Sexual Behavior

What did the study examine? This study examined the relationship between genetics and same-sex sexual behavior. Link to the study.
What year was it published? 2019
Key findings:
1. Both genetic and nongenetic factors play roles in same-sex sexual behavior.
2. While many genetic variants contribute to same-sex sexual behavior, each variant has a small influence. When taken together, the variants explain only a minority of a person’s likelihood of ever engaging in sexual behavior with a person of the same sex, meaning that genetics can never be used to meaningfully predict same-sex sexual behavior.
3. Five loci of genetic variation were significantly associated with same-sex sexual behavior.
4. The variance explained by the polygenic scores for same-sex sexual behavior was extremely low (<1%)
5. Some genetic variants associated with same-sex behavior were also associated with other traits, such as smoking, cannabis use, and risk-taking behavior. 
Corresponding author of FAQ: Brendan Zietsch (zietsch@psy.uq.edu.au)

Miscellaneous

Utility of Polygenic Embryo Screening for Disease Depends on the Selection Strategy

What did the study examine? This study examined the efficacy Polygenic Embryo Screening (PES), i.e., the use of polygenic scores for embryo selection. Link to study
What year was it published? 2021
Key findings:
1. Polygenic scores allow disease risk factors to be assigned to embryos acquired through In-Vitro Fertilization (IVF).
2. Polygenic Embryo Screening (PES) is available for people seeking to select embryos least likely to have specific diseases, such as schizophrenia or Crohn’s disease.
3. There are a number of different selection strategies for using polygenic scores to select embryos.
4. The efficacy of PES is highly contingent on the selection strategy, the accuracy of polygenic scores, and the number of embryos available.
Corresponding author of FAQ: Shai Carmi (shai.carmi@mail.huji.ac.il)
Additional link: https://docs.google.com/document/d/1sOncNOQofKyOBprbgnMDhScqDfi9ELhsCrxUVfCIylw/edit

A Scientometric Review of Genome-Wide Association Studies

What did the study examine? This study examines the “scientometrics” of GWAS, that is: who GWAS researchers are, who funds them, and who (and what) they study. Link to study
What year was it published? 2019
Key findings:
1. 72% of all genetic discoveries come from people living in just three countries: the U.S., U.K., and Iceland.
2. The most frequently studied people in GWAS discoveries are often older and more likely to be female, with large samples consisting of healthy volunteers with a higher socioeconomic status.
3. Over a third (37%) of GWAS authors are female, which is considerably higher than the historical average of women undertaking research in molecular and cell biology (21% from 1665-1989).
4. Over two-thirds (70%) of senior last author positions are men.
Corresponding author of FAQ: Melinda Mills (melinda.mills@nuffield.ox.ac.uk

Screening Human Embryos for Polygenic Traits Has Limited Utility

What did the study examine? This study examined the potential usefulness of embryonic screening for various traits, such as height and IQ. Link to study.
What year was it published? 2019
Key findings:
1. The study found that, given current technology, embryo selection could provide an average gain for 2.5cm height, or 2.5 IQ points for cognitive ability.
Corresponding author of FAQ: Shai Carmi (shai.carmi@huji.ac.il)

Pan-Ancestry Genetic Analysis of the UK Biobank

What did the study examine? In an effort to increase diversity in genetics research and incorporate data that is left out of most genetic analyses, researchers conducted over 16,000 GWAS in samples of individuals residing in the U.K. This ongoing large-scale study is meant to be a starting point for understanding the genetic underpinnings of thousands of traits including height, diabetes, educational attainment, and occupation. Link to project.
What year was it published? 2013
Corresponding author of FAQ: ukb.diverse.gwas@gmail.com