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Cited by 165Genetic Associations and EpidemiologyGenetics and Physical PerformanceNutrition, Genetics, and Disease

Development and Evaluation of a Genetic Risk Score for Obesity

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Belsky, Daniel W., Moffitt, Terrie E., Sugden, Karen, Williams, Benjamin, Houts, Renate, McCarthy, Jeanette, Caspi, Avshalom·2013·Biodemography and Social Biology
DOI 10.1080/19485565.2013.774628PMC PMC3671353
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Abstract

Multi-locus profiles of genetic risk, so-called "genetic risk scores," can be used to translate discoveries from genome-wide association studies into tools for population health research. We developed a genetic risk score for obesity from results of 16 published genome-wide association studies of obesity phenotypes in European-descent samples. We then evaluated this genetic risk score using data from the Atherosclerosis Risk in Communities (ARIC) cohort GWAS sample (N = 10,745, 55% female, 77% white, 23% African American). Our 32-locus GRS was a statistically significant predictor of body mass index (BMI) and obesity among ARIC whites [for BMI, r = 0.13, p<1 × 10(-30); for obesity, area under the receiver operating characteristic curve (AUC) = 0.57 (95% CI 0.55-0.58)]. The GRS predicted differences in obesity risk net of demographic, geographic, and socioeconomic information. The GRS performed less well among African Americans. The genetic risk score we derived from GWAS provides a molecular measurement of genetic predisposition to elevated BMI and obesity.[Supplemental materials are available for this article. Go to the publisher's online edition of Biodemography and Social Biology for the following resource: Supplement to Development & Evaluation of a Genetic Risk Score for Obesity.].

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  • The scientific basis of the imbalance in PRS accuracy has been demonstrated theoretically, in simulations, and empirically across many traits and diseases.

    “The scientific basis of this imbalance has been demonstrated theoretically, in simulations, and empirically across many traits and diseases11–22.”

    From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [19]

    The Results and Discussion report that the obesity genetic risk score predicted BMI and obesity less well among African American than white ARIC participants, supporting an empirical example of unequal accuracy. The paper does not demonstrate the imbalance through simulations or establish it across many traits and diseases; its analysis concerns obesity in these two groups. The indexed passages provide no page numbers. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • PRS are many-fold more accurate in European ancestry individuals than in others, and this disparity is the major ethical and scientific challenge surrounding clinical implementation.

    “However, the major ethical and scientific challenge surrounding clinical implementation is that they are many-fold more accurate in European ancestry individuals than others.”

    From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [19]

    The Results and Discussion (page unavailable) show that this obesity genetic risk score was substantially less predictive in African American than in white ARIC participants. But the study tested one obesity score in those two groups, not PRS generally across all ancestries. Its Discussion does not identify that disparity as the major ethical and scientific challenge to clinical implementation; it instead says the score's modest added predictive value was insufficient to recommend it for clinical risk assessment. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Authors
Belsky, D. W., Moffitt, T. E., Sugden, K., Williams, B., Houts, R., McCarthy, J., & Caspi, A.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • Duke University (US)
  • University of California, San Francisco (US)
Corresponding author
Belsky, Daniel W.
ORCID
Venue
Biodemography and Social Biology
Publisher
Informa UK Limited
Published
2013-01-01
Volume
59
Issue
1
Pages
85-100
ISSN
  • 1948-5565 (ISSN-L)
  • 1948-5573
DOI
10.1080/19485565.2013.774628
PMC
PMC3671353
OpenAlex
W2144333480
Cited by
165
References
78
Citations by year
2026: 3 · 2025: 7 · 2024: 8 · 2023: 23 · 2022: 14 · 2021: 20 · 2020: 14 · 2019: 15 · 2018: 14 · 2017: 10 · 2016: 17 · 2015: 10 · 2014: 8 · 2013: 2
FWCI
8.18
Type
journal article
Language
en
Open access
Locations
  • Biodemography and Social Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
  • Agency for Healthcare Research and Quality (R36HS020524, 1r36hs020524-01)
  • National Institute on Aging (AG-032282, T32AG000029, R01AG032282)
  • National Heart, Lung, and Blood Institute (HHSN268201 100012C, HHSN268201100007I, HHSN268201100007C, HHSN2682 01100008C, HH-SN-268201100006C, HHSN268201100011C, HHSN2682011-00005I, HHSN2682011-­00009I, HHSN268201100005C, HHSN268201100005G, HHSN268201100010C, HHSN268201100011I, R01HL087641, R01HL059367, HHSN26820 1100009C, HHSN2682011-00008I, R01HL086694)
  • National Institute of Mental Health (R01MH077874)
  • National Human Genome Research Institute (U01HG004402)
  • National Center for Research Resources (UL1RR025005)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007376)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
Keywords
polygenic risk score, obesity, body mass index, genome-wide association study, genetic susceptibility, Atherosclerosis Risk in Communities Study, African Americans, obesity prediction
MeSH terms
Black or African American, Family, Female, Humans, Male, Obesity, Phenotype, Prospective Studies, ROC Curve, United States, Body Mass Index, Risk Assessment, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, White People, Atherosclerosis, Genome-Wide Association Study

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