Annual Meeting of the NCI Cohort Consortium (Abstract Submission): Submission #11

serial: '11'
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data:
  additional_authors:
    - add_author_degree: Ph.D.
      add_author_first_name: Daniel
      add_author_last_name: Chasman
      add_author_middle: I
      add_author_organization: "Brigham and Women's Hospital"
    - add_author_degree: ScD
      add_author_first_name: Deirdre
      add_author_last_name: Tobias
      add_author_middle: K
      add_author_organization: "Brigham and Women's Hospital"
  degree_s_: M.S.
  email: rzhang25@bwh.harvard.edu
  first_name: Ruolin
  last_name: Zhang
  organization: "Brigham and Women's Hospital"
  poster_title: "Genetic Risk of Obesity and Low-Carbohydrate Diets on Long-Term Weight Gain: A Gene-Environment Interaction Analysis in the Women's Genome Health Study "
  short_biography_: |
    Background
    Obesity, a modifiable cancer risk factor, drives metabolic dysregulation. Although both genes and diet influence weight gain, it‘s uncertain whether carbohydrate-restricted diets mitigate long-term weight gain and obesity in genetically susceptible individuals. We assessed whether low-carbohydrate diets (LCD) modify the genetic risk of obesity and weight gain.

    Method
    We analyzed the prospective Women’s Genome Health Study with baseline diet, genotyping, lifestyle, and annual self-reported weight (1992–2021). We derived the LCD score (LCDS) by ranking participants’ intake (%kcal/day) of carbohydrate (descending) and fat and protein (ascending). We developed genome-wide (gwPRS) and pathway-specific PRSs (pPRSs) from previous BMI GWAS. Multivariable-adjusted linear regression, Cox, and mixed-effects models tested gene–diet interactions on baseline BMI, incident obesity (BMI≥30kg/m2), and BMI change, with control for multiple testing by effective independent test number (Meff).

    Results
    We analyzed 22,472 women of European ancestry. Baseline carbohydrate intake was 48.9 (SD=7.24) and BMI was 25.9 (4.9). There was a significant LCDS×gwPRS interaction for baseline BMI (β=0.12, 95% CI 0.06–0.17) and BMI change (−0.002, −0.003 to −0.001), but not for incident obesity (HR=0.98, 0.94–1.02), indicating a higher LCDS was related to greater weight gain for women with a higher gwPRS. After multiple testing corrections, 7 KEGG legacy pathways and LCDS interactions remained significant for BMI change.

    Conclusions
    Lower-carbohydrate diets amplified genetic risk for long-term weight gain in women. Future research is needed to clarify diet quality, rather than total carbohydrate restriction, in mitigating weight gain for cancer prevention.
  title: ''