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Quantile-Specific Heritability of Intakes of Alcohol but not Other Macronutrients

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Abstract

Genetic heritability (h2) of alcohol use is reported to be greater in rural dwellers, distressed marriages, low socioeconomic status, in girls who are unmarried or lacking closeness with their parents or religious upbringing, in less-educated men, and in adolescents with peers using alcohol. However, these are all risk factors for heavy drinking, and the greater heritability could be due to quantile-dependent expressivity, i.e., h2 dependent upon whether the phenotype (alcohol intake) is high or low relative to its distribution. Quantile regression showed that h2 estimated from the offspring-parent regression slope increased significantly from lowest to highest gram/day of alcohol consumption (0.006 ± 0.001 per percent, P = 1.1 × 10−7). Heritability at the 90th percentile of the sample distribution (0.557 ± 0.116) was 4.5-fold greater than at the 10th percentile (0.122 ± 0.037). Heritabilities for intakes of other macronutrients were not quantile-dependent. Thus quantile-dependent expressivity may explain the higher estimated heritability associated with risk factors for high alcohol consumption.

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Acknowledgements

The data were obtained from the National Institutes of Health FRAMCOHORT, GEN3, FRAMOFFSPRING Research Materials obtained from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center. The author (PTW) was responsible for the project conception, development of overall research plan, analyzing data including statistical analysis, and wrote the paper. The sole author had responsibility for all parts of the manuscript. The Framingham Heart Study was conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195 and HHSN268201500001I). Funding support for the Framingham Food Frequency Questionnaire dataset was provided by ARS Contract #53- 3k06-5-10, ARS Agreement #’s 58-1950-9-001, 58-1950-4-401 and 58-1950-7-707. This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, FRAMCOHORT, GEN3, FRAMOFFSPRING, Boston University, or NHLBI.

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This research was supported by grant R21ES020700 from the National Institute of Environmental Health Sciences, and an unrestricted gift from HOKA ONE ONE.

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  1. Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Rd, Berkeley, CA, 94720, USA

    Paul T. Williams

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These analyses were approved by Lawrence Berkeley National Laboratory Human Subjects Committee (HSC) for protocol “Gene-environment interaction vs quantile-dependent penetrance of established SNPs (107H021)” LBNL holds Office of Human Research Protections Federal wide Assurance number FWA 00006253. Approval number: 107H021-13MR20.

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Williams, P.T. Quantile-Specific Heritability of Intakes of Alcohol but not Other Macronutrients. Behav Genet 50, 332–345 (2020). https://doi.org/10.1007/s10519-020-10005-z

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