Is the gene-environment interaction paradigm relevant to genome-wide studies? The case of education and body mass index.
- Authors
- Boardman, Jason D; Domingue, Benjamin W; Blalock, Casey L; Haberstick, Brett C; Harris, Kathleen Mullan; McQueen, Matthew B
- Year
- 2014
- Journal
- Demography
- PMID
- 24281739
- DOI
- 10.1007/s13524-013-0259-4
- PMCID
- PMC4035460
This study uses data from the Framingham Heart Study to examine the relevance of the gene-environment interaction paradigm for genome-wide association studies (GWAS). We use completed college education as our environmental measure and estimate the interactive effect of genotype and education on body mass index (BMI) using 260,402 single-nucleotide polymorphisms (SNPs). Our results highlight the sensitivity of parameter estimates obtained from GWAS models and the difficulty of framing genome-wide results using the existing gene-environment interaction typology. We argue that SNP-environment interactions across the human genome are not likely to provide consistent evidence regarding genetic influences on health that differ by environment. Nevertheless, genome-wide data contain rich information about individual respondents, and we demonstrate the utility of this type of data. We highlight the fact that GWAS is just one use of genome-wide data, and we encourage demographers to develop methods that incorporate this vast amount of information from respondents into their analyses.
Conceptual gene-environment interaction models
LLM interpretation
This figure consists of three conceptual line graphs illustrating different gene-environment interaction models: Diathesis-Stress, Differential Susceptibility, and Social Push. Each plot maps Body Mass Index (y-axis) against Genotype (x-axis), comparing a "Healthy environment" (dashed line) and an "Unhealthy environment" (solid line). The models show varying relationships, ranging from a genotype effect present only in unhealthy environments (Diathesis-Stress) to opposing effects based on environment (Differential Susceptibility) and a genotype effect present only in healthy environments (Social Push).
Manhattan and QQ plots for GWGEI-GxE estimates for body mass index
LLM interpretation
This figure consists of a QQ plot (left) and a Manhattan plot (right) showing GWGEI-GxE estimates for body mass index. The QQ plot compares observed versus expected -log10 values, with data points closely following the diagonal line. The Manhattan plot displays -log10 observed values across genomic coordinates (chromosomes 1-22 and X), with a horizontal threshold line at approximately 2.
Top GWGEI results for the GxE parameter estimate
LLM interpretation
This figure consists of six scatter plots with linear regression lines showing the relationship between six different genetic variants (rsIDs) and BMI, stratified by education level ("No college" vs. "College"). The x-axis represents the genotype (0, 1, 2) and the y-axis represents BMI. Each plot includes the Minor Allele Frequency (MAF) and statistical values for genetic effect (PV: G), gene-environment interaction (GxE), and $r^2$.
Distribution of genome-wide association parameter estimates among college graduates and noncollege graduates
LLM interpretation
This figure consists of four scatter plots comparing genome-wide association parameter estimates and p-values between college graduates and noncollege graduates (top row, "True") and two simulated environments (bottom row, "Simulated"). The left panels plot estimates for both groups, dividing the data into eight numbered quadrants via dashed lines, while the right panels plot $-\log_{10}(p)$ values. In all plots, the majority of data points cluster near the origin or along the axes, with a single highlighted black point visible in the "True" data plots.
Distribution of p values from GWGEI models with and without controls for population stratification and gene-environment correlation
LLM interpretation
This figure consists of two scatter plots comparing p-values from GWGEI models. The left panel is a comparison plot showing $-\log_{10}(p)$ values for "Original" models on the x-axis versus "No Pop Strat" models on the y-axis, displaying a dense cluster of points with some dispersion. The right panel is a Quantile-Quantile (Q-Q) plot comparing $-\log_{10}(\text{Observed})$ p-values against $-\log_{10}(\text{Expected})$ p-values, where the data points closely follow the diagonal identity line before deviating upward at higher values.
| Name | Type |
|---|---|
| 5HTTLPR | variant |
| adiposity related genes local | gene |
| Affymetrix 5.0 | drug |
| age | phenotype |
| alcohol | phenotype |
| behavior | phenotype |
| BMI | phenotype |
| body mass index | phenotype |
| body mass phenotypes local | phenotype |
| body weight | phenotype |
| children | cohort |
| college completion | phenotype |
| college degree local | cohort |
| college degree status local | phenotype |
| College education | phenotype |
| college graduates | phenotype |
| Cyp7b1 | gene |
| Danish Twin Registry | cohort |
| delinquency | phenotype |
| DRD4 | gene |
| drug metabolism | phenotype |
| earliest birth cohort local | cohort |
| education | phenotype |
| educational attainment | phenotype |
| energy intake | phenotype |
| environmental status local | phenotype |
| Environmental variance local | phenotype |
| environment (Z) local | drug |
| exercise | phenotype |
| externalizing disorders | phenotype |
| fast-food consumption local | phenotype |
| fast-food restaurants local | phenotype |
| FHS | cohort |
| Framingham Heart Study | cohort |
| Framingham Heart Study Generation 3 local | cohort |
| Framingham Heart Study third generation local | cohort |
| Framingham SHARe local | cohort |
| Framingham SNP Health Association Resource local | cohort |
| G2 sample local | cohort |
| G3 cohort local | cohort |
| gene-environment interaction | phenotype |
| genes | gene |
| genetic factors | cohort |
| genetic makeup (G) local | gene |
| genetic risk | cohort |
| Genetic variance | phenotype |
| Health and Retirement Study | cohort |
| height | phenotype |
| men | cohort |
| most recent birth cohort local | cohort |
| National Longitudinal Study of Adolescent Health | cohort |
| non-college graduates local | cohort |
| non–college graduates local | cohort |
| novelty seeking | phenotype |
| obesity | phenotype |
| obesity-related phenotype | phenotype |
| obesogenic environment local | drug |
| parental mating type local | phenotype |
| parents | cohort |
| phenotypic variance | phenotype |
| physical inactivity | phenotype |
| physical size local | phenotype |
| physical weight local | phenotype |
| poor communities local | phenotype |
| poor neighborhoods local | phenotype |
| Poor neighborhoods local | cohort |
| public exercise outlets local | phenotype |
| relationship status | phenotype |
| Residents local | cohort |
| risk | phenotype |
| risk allele | cohort |
| rs12518350 local | variant |
| rs17005475 local | variant |
| rs4358837 local | variant |
| rs7609257 local | variant |
| sex | phenotype |
| Shared environmental variance local | phenotype |
| single nucleotide polymorphisms | variant |
| skipping breakfast local | phenotype |
| sleep patterns | phenotype |
| smoking | phenotype |
| smoking behavior | phenotype |
| SNP | cohort |
| SNP zone 2 local | variant |
| SNP zone 7 local | variant |
| SNP zones 4 and 5 local | variant |
| socioeconomic status | phenotype |
| substance use | phenotype |
| Swedish Twin Registry | cohort |
| total cholesterol | phenotype |
| United States | cohort |
| weight difference local | phenotype |
| weight gain | phenotype |
| Wisconsin Longitudinal Study local | cohort |
| women | cohort |
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| Discrimination Exposure and Polygenic Risk for Obesity in Adulthood: Testing Gene-Environment Correlations and Interactions. | Cuevas AG et al. | — | 2023 | → |
| Gene-environment interactions and the case of body mass index and obesity: How much do they matter? | Huangfu Y et al. | — | 2023 | → |
| Re-examining the relationship between education and adult mental health in the UK: A research note. | Amin V et al. | — | 2023 | → |
| Education and Cardiovascular Health as Effect Modifiers of APOE ε4 on Dementia: The Atherosclerosis Risk in Communities Study. | Lee M et al. | — | 2022 | → |
| Gene-Environment interactions and the case of BMI and obesity: how much do they matter? | Huangfu Y et al. | — | 2022 | — |
| Polygenic Scores for Plasticity: A New Tool for Studying Gene-Environment Interplay. | Johnson R et al. | — | 2022 | → |
| Achieved educational attainment, inherited genetic endowment for education, and obesity. | Li Y et al. | — | 2021 | → |
| Evaluating the Continued Integration of Genetics into Medical Sociology. | Boardman JD et al. | — | 2021 | → |
| Findings from the Hispanic Community Health Study/Study of Latinos on the Importance of Sociocultural Environmental Interactors: Polygenic Risk Score-by-Immigration and Dietary Interactions. | McArdle CE et al. | — | 2021 | → |
| Identification of genetic loci affecting body mass index through interaction with multiple environmental factors using structured linear mixed model. | Jung HU et al. | — | 2021 | → |
| Insights into non-autoimmune type 1 diabetes with 13 novel loci in low polygenic risk score patients. | Qu J et al. | — | 2021 | → |
| Intersections of Adolescent Well-Being: School, Work, and Weight Status in Brazil. | Marteleto LJ et al. | — | 2021 | → |
| Peer influence on obesity: Evidence from a natural experiment of a gene-environment interaction. | Li Y et al. | — | 2021 | → |
| What have we learned about mortality patterns over the past 25 years? | van Raalte AA | — | 2021 | → |
| Association of a genetic risk score with BMI along the life-cycle: Evidence from several US cohorts. | Sanz-de-Galdeano A et al. | — | 2020 | → |
| A Social Determinant of Health May Modify Genetic Associations for Blood Pressure: Evidence From a SNP by Education Interaction in an African American Population. | Hollister BM et al. | — | 2019 | → |
| Differential vulnerability to neighbourhood disorder: a gene×environment interaction study. | Robinette JW et al. | — | 2019 | → |
| Interaction Effects between the Cumulative Genetic Score and Psychosocial Stressor on Self-Reported Drinking Urge and Implicit Attentional Bias for Alcohol: A Human Laboratory Study. | Kim J et al. | — | 2019 | → |
| Comparing Observed and Unobserved Components of Childhood: Evidence From Finnish Register Data on Midlife Mortality From Siblings and Their Parents. | Kröger H et al. | — | 2018 | → |
| Education, Smoking, and Cohort Change: Forwarding a Multidimensional Theory of the Environmental Moderation of Genetic Effects. | Wedow R et al. | — | 2018 | → |
| Genetics of obesity: what genetic association studies have taught us about the biology of obesity and its complications. | Goodarzi MO | — | 2018 | → |
| Perceived neighborhood social cohesion and cardiometabolic risk: a gene × environment study. | Robinette JW et al. | — | 2018 | → |
| Post-GWAS in Psychiatric Genetics: A Developmental Perspective on the "Other" Next Steps. | Dick DM et al. | — | 2018 | → |
| Schools as Moderators of Genetic Associations with Life Course Attainments: Evidence from the WLS and Add Health. | Trejo S et al. | — | 2018 | → |
| What Can Sociogenomics Learn from <i>Social By Nature</i>? <i>A review of</i> social by nature, <i>by Catherine Bliss</i>. | Daw J et al. | — | 2018 | → |
| Adiposity QTL Adip20 decomposes into at least four loci when dissected using congenic strains. | Lin C et al. | — | 2017 | → |
| Does neighbourhood deprivation affect the genetic influence on body mass? | Owen G et al. | — | 2017 | → |
| Genetic Heterogeneity in Depressive Symptoms Following the Death of a Spouse: Polygenic Score Analysis of the U.S. Health and Retirement Study. | Domingue BW et al. | — | 2017 | → |
| Between (Racial) Groups and a Hard Place: An Exploration of Social Science Approaches to Race and Genetics, 2000-2014. | Byrd WC et al. | — | 2016 | → |
| Differential Vulnerability to Early-Life Parental Death: The Moderating Effects of Family Suicide History on Risks for Major Depression and Substance Abuse in Later Life. | Hollingshaus MS et al. | — | 2016 | → |
| Gender and genetic contributions to weight identity among adolescents and young adults in the U.S. | Wedow R et al. | — | 2016 | → |
| Limitations of GCTA as a solution to the missing heritability problem. | Krishna Kumar S et al. | — | 2016 | → |
| Molecular genetic approaches to understanding the comorbidity of psychiatric disorders. | Gizer IR | — | 2016 | → |
| Opportunities and challenges of big data for the social sciences: The case of genomic data. | Liu H et al. | — | 2016 | → |
| Candidate gene-environment interaction research: reflections and recommendations. | Dick DM et al. | — | 2015 | → |
| Lifetime Socioeconomic Status, Historical Context, and Genetic Inheritance in Shaping Body Mass in Middle and Late Adulthood. | Liu H et al. | — | 2015 | → |
| The Genome-Wide Influence on Human BMI Depends on Physical Activity, Life Course, and Historical Period. | Guo G et al. | — | 2015 | → |
| The National Longitudinal Study of Adolescent to Adult Health (Add Health) sibling pairs genome-wide data. | McQueen MB et al. | — | 2015 | → |
| Gene-age interactions in blood pressure regulation: a large-scale investigation with the CHARGE, Global BPgen, and ICBP Consortia. | Simino J et al. | — | 2014 | → |
| Gene-environment interaction research in psychiatric epidemiology: a framework and implications for study design. | Belsky DW et al. | — | 2014 | → |
| Integrating genetics and social science: genetic risk scores. | Belsky DW et al. | — | 2014 | → |
| Polygenic risk predicts obesity in both white and black young adults. | Domingue BW et al. | — | 2014 | → |