Browsing by Author "Williams, Benjamin S"
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Item Unknown Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm.(eLife, 2020-05-05) Belsky, Daniel W; Caspi, Avshalom; Arseneault, Louise; Baccarelli, Andrea; Corcoran, David L; Gao, Xu; Hannon, Eiliss; Harrington, Hona Lee; Rasmussen, Line Jh; Houts, Renate; Huffman, Kim; Kraus, William E; Kwon, Dayoon; Mill, Jonathan; Pieper, Carl F; Prinz, Joseph A; Poulton, Richie; Schwartz, Joel; Sugden, Karen; Vokonas, Pantel; Williams, Benjamin S; Moffitt, Terrie EBiological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is sensitive to variation in pace of biological aging among individuals born the same year. We first modeled change-over-time in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in n = 954 members of the Dunedin Study born in 1972-1973. Rates of change in each biomarker over ages 26-38 years were composited to form a measure of aging-related decline, termed Pace-of-Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace-of-Aging, called DunedinPoAm for Dunedin(P)ace(o)f(A)ging(m)ethylation. Validation analysis in cohort studies and the CALERIE trial provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person's pace of biological aging.Item Unknown The Genetics of Success: How Single-Nucleotide Polymorphisms Associated With Educational Attainment Relate to Life-Course Development.(Psychol Sci, 2016-07) Belsky, Daniel W; Moffitt, Terrie E; Corcoran, David L; Domingue, Benjamin; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sugden, Karen; Williams, Benjamin S; Poulton, Richie; Caspi, AvshalomA previous genome-wide association study (GWAS) of more than 100,000 individuals identified molecular-genetic predictors of educational attainment. We undertook in-depth life-course investigation of the polygenic score derived from this GWAS using the four-decade Dunedin Study (N = 918). There were five main findings. First, polygenic scores predicted adult economic outcomes even after accounting for educational attainments. Second, genes and environments were correlated: Children with higher polygenic scores were born into better-off homes. Third, children's polygenic scores predicted their adult outcomes even when analyses accounted for their social-class origins; social-mobility analysis showed that children with higher polygenic scores were more upwardly mobile than children with lower scores. Fourth, polygenic scores predicted behavior across the life course, from early acquisition of speech and reading skills through geographic mobility and mate choice and on to financial planning for retirement. Fifth, polygenic-score associations were mediated by psychological characteristics, including intelligence, self-control, and interpersonal skill. Effect sizes were small. Factors connecting DNA sequence with life outcomes may provide targets for interventions to promote population-wide positive development.