Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals

Lee, James J.; Wedow, Robbee; Okbay, Aysu; Kong, Edward; Maghzian, Omeed; Zacher, Meghan; Nguyen-Viet, Tuan Anh; Bowers, Peter N.; Sidorenko, Julia; Linnér, Richard Karlsson; Fontana, Mark Alan; Kundu, Tushar; Lee, Chan Wook; Li, Hui; Li, Ruoxi; Royer, Rebecca; Timshel, Pascal; Walters, Raymond; Willoughby, Emily A.; Yengo, Loïc; Alver, Maris; Bao, Yanchun; Clark, David W.; Day, Felix R.; Furlotte, Nicholas A.; Joshi, Peter K.; Kemper, Kathryn E.; Kleinman, Aaron; Langenberg, Claudia; Mägi, Reedik; Trampush, Joey W.; Verma, Shefali S.; Wu, Yang; Lam, Max; Zhao, Jing Hua; Zheng, Zhili; Boardman, Jason D.; Campbell, Harry; Freese, Jeremy; Harris, Kathleen Mullan; Hayward, Caroline; Herd, Pamela; Kumari, Meena; Lencz, Todd; Luan, Jian’an; Malhotra, Anil K.; Metspalu, Andres; Milani, Lili; Ong, Ken K.; Perry, John R. B.; Porteous, David J.; Ritchie, Marylyn D.; Smart, Melissa; Smith, Blair H.; Tung, Joyce Y.; Wareham, Nicholas J.; Wilson, James F.; Beauchamp, Jonathan P.; Conley, Dalton; Esko, Tõnu; Lehrer, Steven F.; Magnusson, Patrik K. E.; Oskarsson, Sven; Pers, Tune H.; Robinson, Matthew R.; Thom, Kevin; Watson, Chelsea; Chabris, Christopher F.; Meyer, Michelle N.; Laibson, David; Yang, Jian; Johannesson, Magnus; Koellinger, Philipp; Turley, Patrick; Visscher, Peter M.; Benjamin, Daniel J.; Cesarini, David

doi:10.1038/s41588-018-0147-3

Cited by 2,222 publications

(2,995 citation statements)

References 55 publications

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“…These weighted NEO PI‐R/3 (a) domain and (b) facet scores were then averaged, yielding either DRS or FRS. We included all NEO PI‐R/3 domains in DRS and all facets in FRS regardless of the magnitude or significance of their respective meta‐analytic weights, as many papers working on polygenic risk scores have shown that the best prediction can generally be achieved when all predictors are included in risk scores, no matter the effect size . The observed BMI was then predicted from the DRS and FRS (all expressed in z scores), controlling for sex, age, age 2 , and education.…”

Section: Methodsmentioning

confidence: 99%

“…The poly‐trait risk score represents as much variance in BMI that can be collectively predicted by the set of traits, be they domains or facets. This approach has already been successfully used in personality research, and it is conceptually very similar to polygenic risk scores widely used in genetics . We expect FRS to explain more variance in BMI than DRS.…”

Section: Introductionmentioning

confidence: 99%

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Personality‐obesity associations are driven by narrow traits: A meta‐analysis

et al. 2019

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Summary Obesity has inconsistent associations with broad personality domains, possibly because the links pertain to only some facets of these domains. Collating published and unpublished studies (N = 14 848), we meta‐analysed the associations between body mass index (BMI) and Five‐Factor Model personality domains as well as 30 Five‐Factor Model personality facets. At the domain level, BMI had a positive association with Neuroticism and a negative association with Conscientiousness domains. At the facet level, we found associations between BMI and 15 facets from all five personality domains, with only some Neuroticism and Conscientiousness facets among them. Certain personality‐BMI associations were moderated by sample properties, such as proportions of women or participants with obesity; these moderation effects were replicated in the individual‐level analysis. Finally, facet‐based personality “risk” scores accounted for 2.3% of variance in BMI in a separate sample of individuals (N = 3569), 409% more than domain‐based scores. Taken together, personality‐BMI associations are facet specific, and delineating them may help to explain obesity‐related behaviours and inform intervention designs. Preprint and data are available at https://psyarxiv.com/z35vn/.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Personality‐obesity associations are driven by narrow traits: A meta‐analysis

et al. 2019

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“…As such, these individuals may have greater scholastic aspirations and be more likely to seek out educational opportunities beyond high school. Across studies, the variance accounted for by polygenic contributions for educational attainment and higher education has ranged from 2% to 13% . Variability in the variance accounted for by the EA PGS across studies may be due to differences in the sizes of the discovery samples, with smaller discovery samples yielding less robust effect sizes.…”

Section: Introductionmentioning

confidence: 99%

Associations between an educational attainment polygenic score with educational attainment in an African American sample

Rabinowitz

Kuo

Felder

et al. 2019

Genes Brain and Behavior

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Polygenic propensity for educational attainment has been associated with higher education attendance, academic achievement and criminal offending in predominantly European samples; however, less is known about whether this polygenic propensity is associated with these outcomes among African Americans. Using an educational attainment polygenic score (EA PGS), the present study examined whether this score was associated with post‐secondary education, academic achievement and criminal offending in an urban, African American sample. Three cohorts of participants (N = 1050; 43.9% male) were initially recruited for an elementary school‐based universal prevention trial in a Mid‐Atlantic city and followed into young adulthood. Standardized tests of reading and math achievement were administered in first grade. At age 20, participants reported on their level of education attained, and records of incarceration were obtained from Maryland's Criminal Justice Information System. In young adulthood, DNA was collected and extracted from blood or buccal swabs and genotyped. An EA PGS was created using results from a large‐scale genome‐wide association study on educational attainment. A higher EA PGS was associated with a greater log odds of post‐secondary education. The EA PGS was not associated with reading achievement, although a significant relationship was found with math achievement in the third cohort. These findings contribute to the dearth of molecular genetics work conducted in African American samples and highlight that polygenic propensity for educational attainment is associated with higher education attendance.

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“…Modern research has shown that such traits are shaped through gene × environment interactions, epigenetics, environment, and chance (Caspi & Moffitt, ; Enoch, ; Graves, ; Haberstick et al, ; Keller, ; MacMahon, ; Okbay et al, ). Moreover, genome‐wide association studies have established that only 0.01–0.035% of the variability in educational attainment is associated with any single gene variant (23andMe Research Team et al, ; Okbay et al, ). The combined contribution of all of these genomic variants to any group level difference in a complex human trait is predicted to be small, possibly spurious, and largely dependent on the environment according to population genetic theory (Rosenberg et al, ).…”

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confidence: 99%

Toward a more humane genetics education: Learning about the social and quantitative complexities of human genetic variation research could reduce racial bias in adolescent and adult populations

Donovan

Semmens

Keck³

et al. 2019

Science Education

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When people are exposed to information that leads them to overestimate the actual amount of genetic difference between racial groups, it can augment their racial biases. However, there is apparently no research that explores if the reverse is possible. Does teaching adolescents scientifically accurate information about genetic variation within and between US census races reduce their racial biases? We randomized 8th and 9th grade students (n = 166) into separate classrooms to learn for an entire week either about the topics of (a) human genetic variation or (b) climate variation. In a cross‐over randomized trial with clustering, we demonstrate that when students learn about genetic variation within and between racial groups it significantly changes their perceptions of human genetic variation, thereby causing a significant decrease in their scores on instruments assessing cognitive forms of prejudice. We then replicate these findings in two computer‐based randomized controlled trials, one with adults (n = 176) and another with biology students (n = 721, 9th–12th graders). These results indicate that teaching about human variation in the domain of genetics has potentially powerful effects on social cognition during adolescence. In turn, we argue that learning about the social and quantitative complexities of human genetic variation research could prepare students to become informed participants in a society where human genetics is invoked as a rationale in sociopolitical debates.

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Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals

Cited by 2,222 publications

References 55 publications

Personality‐obesity associations are driven by narrow traits: A meta‐analysis

Personality‐obesity associations are driven by narrow traits: A meta‐analysis

Associations between an educational attainment polygenic score with educational attainment in an African American sample

Toward a more humane genetics education: Learning about the social and quantitative complexities of human genetic variation research could reduce racial bias in adolescent and adult populations

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