Dataset Information

Parent-offspring inference in inbred populations.

ABSTRACT: Genealogical relationships are fundamental components of genetic studies. However, it is often challenging to infer correct and complete pedigrees even when genome-wide information is available. For example, inbreeding can obscure genetic differences between individuals, making it difficult to even distinguish first-degree relatives such as parent-offspring from full siblings. Similarly, genotyping errors can interfere with the detection of genetic similarity between parents and their offspring. Inbreeding is common in natural, domesticated, and experimental populations and genotyping of these populations often has more errors than in human data sets, so efficient methods for building pedigrees under these conditions are necessary. Here, we present a new method for parent-offspring inference in inbred pedigrees called specific parent-offspring relationship estimation (spore). spore is vastly superior to existing pedigree-inference methods at detecting parent-offspring relationships, in particular when inbreeding is high or in the presence of genotyping errors, or both. spore therefore fills an important void in the arsenal of pedigree inference tools.

SUBMITTER: Runge JN

PROVIDER: S-EPMC9796703 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Parent-offspring inference in inbred populations.

Runge Jan-Niklas JN König Barbara B Lindholm Anna K AK Bendesky Andres A

Molecular ecology resources 20220722 8

Genealogical relationships are fundamental components of genetic studies. However, it is often challenging to infer correct and complete pedigrees even when genome-wide information is available. For example, inbreeding can obscure genetic differences between individuals, making it difficult to even distinguish first-degree relatives such as parent-offspring from full siblings. Similarly, genotyping errors can interfere with the detection of genetic similarity between parents and their offspring. ...[more]

PMID: 35770342

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Project description:ImportancePrevious studies have shown an inverse association between offspring religiosity and suicidal ideation/attempts, but the association of parent religiosity on offspring suicidal ideation/attempts has not been examined.ObjectiveTo examine associations of parent and offspring religiosity with suicide ideation and attempts in offspring.Design, setting, and participantsThe study is based on offspring (generation 3) from a 3-generation family study at New York State Psychiatric Institute and Columbia University, in which generations 2 and 3 were defined as being at high risk or low risk for major depressive disorder because of the presence or absence of major depressive disorder in generation 1. The association between suicidal behaviors (ideation/attempts) and parent and offspring religiosity in generation 3 offspring aged 6 to 18 years (214 offspring from 112 nuclear families) was examined.Main outcomes and measuresParents' psychiatric diagnoses and suicidal behaviors were assessed with the Schedule for Affective Disorders and Schizophrenia, and offspring were independently assessed using the child version. Two measures of religiosity were assessed: religious importance and religious attendance. Logistic regressions in the framework of generalized estimation equations were performed to analyze offspring suicidal behaviors while adjusting for sibling correlation and offspring age, sex, and familial depression risk status.ResultsOf 214 offspring, 112 (52.3%) were girls. Offspring religious importance was associated with a lower risk for suicidal behavior in girls (odds ratio [OR], 0.48; 95% CI, 0.33-0.70) but not in boys (OR, 1.15; 95% CI, 0.74-1.80) (religiosity by sex interaction, P = .05). Religious attendance was associated with a lower risk for suicidal behavior in girls (OR, 0.64; 95% CI, 0.49-0.84) but not boys (OR, 0.94; 95% CI, 0.69-1.27) (religiosity by sex interaction, P = .17). Parent religious importance was associated with a lower risk for offspring suicidal behavior (OR, 0.61; 95% CI, 0.41-0.91) but not parent religious attendance. When parent and offspring religious importance were considered simultaneously, we found a lower risk associated with parental religious importance (OR, 0.61; 95% CI, 0.39-0.96) independent of offspring importance. These associations were independent of parental depression, marital status, and parental suicide ideation.Conclusions and relevanceIn this study, parental belief in religious importance was associated with lower risk for suicidal behavior in offspring independent of an offspring's own belief about religious importance and other known parental factors, such as parental depression, suicidal behavior, and divorce.

Project description:Introduction: In genetic epidemiology, log-linear models of population risk may be used to study the effect of genotypes and exposures on the relative risk of a disease. Such models may also include gene-environment interaction terms that allow the genotypes to modify the effect of the exposure, or equivalently, the exposure to modify the effect of genotypes on the relative risk. When a measured test locus is in linkage disequilibrium with an unmeasured causal locus, exposure-related genetic structure in the population can lead to spurious gene-environment interaction; that is, to apparent gene-environment interaction at the test locus in the absence of true gene-environment interaction at the causal locus. Exposure-related genetic structure occurs when the distributions of exposures and of haplotypes at the test and causal locus both differ across population strata. A case-parent trio design can protect inference of genetic main effects from confounding bias due to genetic structure in the population. Unfortunately, when the genetic structure is exposure-related, the protection against confounding bias for the genetic main effect does not extend to the gene-environment interaction term. Methods: We show that current methods to reduce the bias in estimated gene-environment interactions from case-parent trio data can only account for simple population structure involving two strata. To fill this gap, we propose to directly accommodate multiple population strata by adjusting for genetic principal components (PCs). Results and Discussion: Through simulations, we show that our PC adjustment maintains the nominal type-1 error rate and has nearly identical power to detect gene-environment interaction as an oracle approach based directly on population strata. We also apply the PC-adjustment approach to data from a study of genetic modifiers of cleft palate comprised primarily of case-parent trios of European and East Asian ancestry. Consistent with earlier analyses, our results suggest that the gene-environment interaction signal in these data is due to the self-reported European trios.

Dataset Information

Parent-offspring inference in inbred populations.

Publications

Parent-offspring inference in inbred populations.

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