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1.
Science ; 365(6456)2019 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-31467194

RESUMO

Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in same-sex sexual behavior, only partially overlapped between males and females, and do not allow meaningful prediction of an individual's sexual behavior. Comparing these GWAS results with those for the proportion of same-sex to total number of sexual partners among nonheterosexuals suggests that there is no single continuum from opposite-sex to same-sex sexual behavior. Overall, our findings provide insights into the genetics underlying same-sex sexual behavior and underscore the complexity of sexuality.

3.
Nat Genet ; 51(8): 1295, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31239548

RESUMO

In the version of the paper initially published, no competing interests were declared. The 'Competing interests' statement should have stated that B.M.N. is on the Scientific Advisory Board of Deep Genomics. The error has been corrected in the HTML and PDF versions of the article.

4.
Nat Genet ; 51(2): 245-257, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30643258

RESUMO

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated ([Formula: see text] ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.


Assuntos
Comportamento/fisiologia , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Estudos de Casos e Controles , Feminino , Genética Comportamental/métodos , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética
5.
Nat Genet ; 51(2): 237-244, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30643251

RESUMO

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Fumar/genética , Tabagismo/genética , Feminino , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Risco , Tabaco/efeitos adversos
6.
Nat Genet ; 50(8): 1112-1121, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30038396

RESUMO

Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.

7.
Proc Natl Acad Sci U S A ; 115(31): E7275-E7284, 2018 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-29987013

RESUMO

A summary genetic measure, called a "polygenic score," derived from a genome-wide association study (GWAS) of education can modestly predict a person's educational and economic success. This prediction could signal a biological mechanism: Education-linked genetics could encode characteristics that help people get ahead in life. Alternatively, prediction could reflect social history: People from well-off families might stay well-off for social reasons, and these families might also look alike genetically. A key test to distinguish biological mechanism from social history is if people with higher education polygenic scores tend to climb the social ladder beyond their parents' position. Upward mobility would indicate education-linked genetics encodes characteristics that foster success. We tested if education-linked polygenic scores predicted social mobility in >20,000 individuals in five longitudinal studies in the United States, Britain, and New Zealand. Participants with higher polygenic scores achieved more education and career success and accumulated more wealth. However, they also tended to come from better-off families. In the key test, participants with higher polygenic scores tended to be upwardly mobile compared with their parents. Moreover, in sibling-difference analysis, the sibling with the higher polygenic score was more upwardly mobile. Thus, education GWAS discoveries are not mere correlates of privilege; they influence social mobility within a life. Additional analyses revealed that a mother's polygenic score predicted her child's attainment over and above the child's own polygenic score, suggesting parents' genetics can also affect their children's attainment through environmental pathways. Education GWAS discoveries affect socioeconomic attainment through influence on individuals' family-of-origin environments and their social mobility.


Assuntos
Estudo de Associação Genômica Ampla , Classe Social , Mobilidade Social , Escolaridade , Testes Genéticos , Humanos , Estudos Longitudinais , Ocupações , Irmãos
8.
Soc Forces ; 96(3): 1377-1409, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29681662

RESUMO

This paper uses data from The National Longitudinal Study of Adolescent to Adult Health (Add Health) to describe county-level variation in norms regarding physical weight among adolescents in the United States. We demonstrate that regardless of one's physical size, those residing in counties with a heavier weight norm are significantly less likely to see themselves as overweight than those residing in counties with a light weight norm. We further show that the local weight norm during adolescence (Wave 1) is associated with individuals' weight perceptions through adolescence and into young adulthood (Wave 4), though these associations attenuate in strength as respondents age. Our results suggest that weight norms have a stronger influence on weight perceptions among women compared to men and that the role of gender is particularly important during adolescence. We encourage life course researchers to consider the normative health environment during adolescence as an important context for understanding disparities in health and health lifestyles as people age.

9.
Nat Genet ; 50(2): 229-237, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29292387

RESUMO

We introduce multi-trait analysis of GWAS (MTAG), a method for joint analysis of summary statistics from genome-wide association studies (GWAS) of different traits, possibly from overlapping samples. We apply MTAG to summary statistics for depressive symptoms (N eff = 354,862), neuroticism (N = 168,105), and subjective well-being (N = 388,538). As compared to the 32, 9, and 13 genome-wide significant loci identified in the single-trait GWAS (most of which are themselves novel), MTAG increases the number of associated loci to 64, 37, and 49, respectively. Moreover, association statistics from MTAG yield more informative bioinformatics analyses and increase the variance explained by polygenic scores by approximately 25%, matching theoretical expectations.

10.
Soc Sci Med ; 165: 99-107, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27500942

RESUMO

In this paper, we investigate the possibility that genetic variation contributes to self-perceived weight status among adolescents and young adults in the U.S. Using samples of identical and fraternal twins across four waves of the National Longitudinal Study of Adolescent to Adult Health (Add Health) study, we calculate heritability estimates for objective body mass index (BMI) that are in line with previous estimates. We also show that perceived weight status is heritable (h(2) ∼ 0.47) and most importantly that this trait continues to be heritable above and beyond objective BMI (h(2) ∼ 0.25). We then demonstrate significant sex differences in the heritability of weight identity across the four waves of the study, where h(2)women = 0.39, 0.35, 0.40, and 0.50 for each wave, respectively, and h(2)men = 0.10, 0.10, 0.23, and 0.03. These results call for a deeper consideration of both identity and gender in genetics research.


Assuntos
Comportamento do Adolescente/psicologia , Peso Corporal , Identidade de Gênero , Percepção , Adolescente , Índice de Massa Corporal , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Estudos em Gêmeos como Assunto , Gêmeos Dizigóticos/psicologia , Gêmeos Monozigóticos/psicologia , Estados Unidos , Adulto Jovem
11.
Biodemography Soc Biol ; 62(1): 1-18, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27050030

RESUMO

An increasing number of studies that are widely used in the demographic research community have collected genome-wide data from their respondents. It is therefore important that demographers have a proper understanding of some of the methodological tools needed to analyze such data. This article details the underlying methodology behind one of the most common techniques for analyzing genome-wide data, genome-wide complex trait analysis (GCTA). GCTA models provide heritability estimates for health, health behaviors, or indicators of attainment using data from unrelated persons. Our goal was to describe this model, highlight the utility of the model for biodemographic research, and demonstrate the performance of this approach under modifications to the underlying assumptions. The first set of modifications involved changing the nature of the genetic data used to compute genetic similarities between individuals (the genetic relationship matrix). We then explored the sensitivity of the model to heteroscedastic errors. In general, GCTA estimates are found to be robust to the modifications proposed here, but we also highlight potential limitations of GCTA estimates.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Característica Quantitativa Herdável , Conjuntos de Dados como Assunto , Variação Genética , Humanos , Modelos Genéticos
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