Biology subjects

Domingue, B. W.

Publications and source records attributed to Domingue, B. W..

5 recordsLinked to original sources

bioRxiv2018

Genetics & the Geography of Health, Behavior, and Attainment

Peoples life chances can be predicted by their neighborhoods. This observation is driving efforts to improve lives by changing neighborhoods. Some neighborhood effects may be causal, supporting neighborhood-level interventions. Other neighborhood effects may reflect selection of families with different characteristics into different neighborhoods, supporting interventions that target families/individuals directly. To test how selection affects different neighborhood-linked problems, we linked neighborhood data with genetic, health, and social-outcome data for >7,000 European-descent UK and US young people in the E-Risk and Add Health Studies. We tested selection/concentration of genetic risks for obesity, schizophrenia, teen-pregnancy, and poor educational outcomes in high-risk neighborhoods, including genetic analysis of neighborhood mobility. Findings argue against genetic selection/concentration as an explanation for neighborhood gradients in obesity and mental-health problems, suggesting neighborhoods may be causal. In contrast, modest genetic selection/concentration was evident for teen-pregnancy and poor educational outcomes, suggesting neighborhood effects for these outcomes should be interpreted with care.

genetics↗

bioRxiv2017

A family-based method for leveraging random genetic variation to identify variance-controlling loci

The propensity of a trait to vary within a population may have evolutionary, ecological, or clinical significance. In the present study we deploy sibling models to offer a novel and unbiased way to ascertain loci associated with the extent to which phenotypes vary (variance-controlling quantitative trait loci, or vQTLs). Previous methods for vQTL-mapping either exclude genetically related individuals or treat genetic relatedness among individuals as a complicating factor addressed by adjusting estimates for non-independence in phenotypes. The present method uses genetic relatedness as a tool to obtain unbiased estimates of variance effects rather than as a nuisance. The family-based approach, which utilizes random variation between siblings in minor allele counts at a locus, also allows controls for parental genotype, mean effects, and non-linear (dominance) effects that may spuriously appear to generate variation.\n\nSimulations show that the approach performs equally well as two existing methods (squared Z-score and DGLM) in controlling type I error rates when there is no unobserved confounding, and performs significantly better than these methods in the presence of confounding. Using height and BMI as empirical applications, we investigate SNPs that alter within-family variation in height and BMI, as well as pathways that appear to be enriched. One significant SNP for BMI variability, in the MAST4 gene, replicated. Pathway analysis revealed one gene set, encoding members of several signaling pathways related to gap junction function, which appears significantly enriched for associations with within-family height variation in both datasets (while not enriched in analysis of mean levels). We recommend approximating laboratory random assignment of genotype using family data and more careful attention to the possible conflation of mean and variance effects.

genetics↗

bioRxiv2017

Father Absence And Accelerated Reproductive Development

Evidence shows that girls who experience father absence in childhood experience accelerated reproductive development in comparison to peers with present fathers. One hypothesis advanced to explain this empirical pattern is genetic confounding, wherein gene-environment correlation (rGE) causes a spurious relationship between father absence and reproductive timing. We test this hypothesis by constructing polygenic scores for age at menarche and first birth using recently available genome wide association study results and molecular genetic data on a sample of non-Hispanic white females from the National Longitudinal Study of Adolescent to Adult Health. Young womens accelerated menarche polygenic scores were unrelated to their exposure to father absence. In contrast, earlier first-birth polygenic scores tended to be higher in young women raised in homes with absent fathers. Nevertheless, father absence and the polygenic scores independently and additively predict reproductive timing. We find limited evidence in support of the gene-environment correlation hypothesis.

genetics↗

bioRxiv2017

Analysis of genetic similarity among friends and schoolmates in the National Longitudinal Study of Adolescent to Adult Health (Add Health)

Humans tend to form social relationships with others who resemble them. Whether this sorting of like with like arises from historical patterns of migration, meso-level social structures in modern society, or individual-level selection of similar peers remains unsettled. Recent research has evaluated the possibility that unobserved genotypes may play an important role in the creation of homophilous relationships. We extend this work by using data from 9,500 adolescents from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to examine genetic similarities among pairs of friends. While there is some evidence that friends have correlated genotypes, both at the whole-genome level as well as at trait-associated loci (via polygenic scores), further analysis suggests that meso-level forces, such as school assignment, are a principal source of genetic similarity between friends. We also observe apparent social-genetic effects in which polygenic scores of an individuals friends and schoolmates predict the individuals own educational attainment. In contrast, an individuals height is unassociated with the height genetics of peers.\n\nSignificanceOur study reported significant findings of a \"social genome\" that can be quantified and studied to understand human health and behavior. In a national sample of more than 9,000 American adolescents, we found evidence of social forces that act to make friends and schoolmates more genetically similar to one another as compared to random pairs of unrelated individuals. This subtle genetic similarity was observed across the entire genome and at sets of genomic locations linked with specific traits--educational attainment and body-mass index--a phenomenon we term \"social-genetic correlation.\" We also find evidence of a \"social-genetic effect\" such that the genetics of a persons friends and schoolmates influenced their own education, even after accounting for the persons own genetics.

genetics↗

bioRxiv2016

A broad sense measure of health and its properties in the HRS

Measuring health is a crucial component of much social research. Two approaches are typical. Health may be measured via either narrowly targeted questions about aspects of disability or chronic conditions. Alternatively, individuals may be asked to self-report their health in some global sense. Both approaches have potential drawbacks. We consider a broad sense measure of health constructed by items from five different batteries related to physical and mental wellbeing. We demonstrate that this measure predicts time until death better than self-reported health, especially for females. Although this measure has promise, we argue that future surveys on health would benefit from the inclusion of additional items focusing on issues salient to younger individuals or other non-disabled respondents.

epidemiology↗