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Association of a Genetic Risk Score With Body Mass Index Across Different Birth Cohorts

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Walter, Stefan, Mejía-Guevara, Iván, Estrada, Karol, Liu, Sze Y., Glymour, M. Maria·2016·JAMA
DOI 10.1001/jama.2016.8729
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Abstract

IMPORTANCE: Many genetic variants are associated with body mass index (BMI). Associations may have changed with the 20th century obesity epidemic and may differ for black vs white individuals. OBJECTIVE: Using birth cohort as an indicator for exposure to obesogenic environment, to evaluate whether genetic predisposition to higher BMI has a larger magnitude of association among adults from more recent birth cohorts, who were exposed to the obesity epidemic at younger ages. DESIGN, SETTING, AND PARTICIPANTS: Observational study of 8788 adults in the US national Health and Retirement Study who were aged 50 years and older, born between 1900 and 1958, with as many as 12 BMI assessments from 1992 to 2014. EXPOSURES: A multilocus genetic risk score for BMI (GRS-BMI), calculated as the weighted sum of alleles of 29 single nucleotide polymorphisms associated with BMI, with weights equal to the published per-allele effects. The GRS-BMI represents how much each person's BMI is expected to differ, based on genetic background (with respect to these 29 loci), from the BMI of a sample member with median genetic risk. The median-centered GRS-BMI ranged from -1.68 to 2.01. MAIN OUTCOMES AND MEASURES: BMI based on self-reported height and weight. RESULTS: GRS-BMI was significantly associated with BMI among white participants (n = 7482; mean age at first assessment, 59 years; 3373 [45%] were men; P <.001) and among black participants (n = 1306; mean age at first assessment, 57 years; 505 [39%] were men; P <.001) but accounted for 0.99% of variation in BMI among white participants and 1.37% among black participants. In multilevel models accounting for age, the magnitude of associations of GRS-BMI with BMI were larger for more recent birth cohorts. For example, among white participants, each unit higher GRS-BMI was associated with a difference in BMI of 1.37 (95% CI, 0.93 to 1.80) if born after 1943, and 0.17 (95% CI, -0.55 to 0.89) if born before 1924 (P = .006). For black participants, each unit higher GRS-BMI was associated with a difference in BMI of 3.70 (95% CI, 2.42 to 4.97) if born after 1943, and 1.44 (95% CI, -1.40 to 4.29) if born before 1924. CONCLUSIONS AND RELEVANCE: For participants born between 1900 and 1958, the magnitude of association between BMI and a genetic risk score for BMI was larger among persons born in later cohorts. This suggests that associations of known genetic variants with BMI may be modified by obesogenic environments.

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Metadata

Authors
Walter, S., Mejía-Guevara, I., Estrada, K., Liu, S. Y., & Glymour, M. M.
Affiliations
  • University of California, San Francisco (US)
  • Harvard Center for Population and Development Studies, Harvard University, Cambridge, Massachusetts
  • Broad Institute (US)
  • Harvard University (US)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2016-07-05
Volume
316
Issue
1
Pages
63
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2016.8729
OpenAlex
W2466503433
Cited by
130
References
0
Citations by year
2026: 6 · 2025: 4 · 2024: 8 · 2023: 11 · 2022: 13 · 2021: 8 · 2020: 18 · 2019: 14 · 2018: 21 · 2017: 17 · 2016: 8
FWCI
16.16
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (U01AG009740, RC2AG036495, and RC4AG039029, RC2AG036495, and RC4AG039029, RC4AG039029, U01AG009740)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
Keywords
polygenic risk score, body mass index, obesity, birth cohort, obesogenic environment, obesity epidemic, single nucleotide polymorphisms, genetic predisposition to obesity, racial differences, Black and White adults, older adults, Health and Retirement Study, gene-environment interaction
MeSH terms
Age Factors, Aged, Aged, 80 and over, Alleles, Black or African American, Female, Humans, Male, Middle Aged, Obesity, Risk Factors, United States, Genetic Variation, Cohort Studies, Body Mass Index, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Black People, White People, Genome-Wide Association Study, Multilocus Sequence Typing

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