Dataset Information

Application of the regression of offspring on mid-parent method to detect associations between single-nucleotide polymorphisms and the beta 2 electroencephalogram phenotype in the COGA data.

ABSTRACT: The beta 2 electroencephalogram (EEG) phenotype is used as a quantitative measure related to alcoholism, and evidence of linkage and association has previously been reported in the Collaborative Study on the Genetics of Alcoholism data. In this study, associations between the beta 2 EEG phenotype and single nucleotide polymorphisms from whole-genome Illumina and Affymetrix panels were investigated with the regression of offspring on mid-parent method to identify significant genetic effects and to estimate their heritability. Separate regressions on father and mother were performed to identify parent-specific effects. Estimates of the heritability of the beta 2 EEG phenotype were 0.68 +/- 0.12 and 0.52 +/- 0.07 based on father-offspring and mother-offspring pairs, respectively. Significant associations at the 0.0005 level, some of which were parent-specific, were found on chromosomes 1, 2, 5, 6, 7, 8, 11, 12, 15, 16, 17, 18, and 19 with heritability attributable to each SNP ranging from 0.01 to 8%.

SUBMITTER: Roy-Gagnon MH

PROVIDER: S-EPMC1866727 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature

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Application of the regression of offspring on mid-parent method to detect associations between single-nucleotide polymorphisms and the beta 2 electroencephalogram phenotype in the COGA data.

Roy-Gagnon Marie-Hélène MH Mathias Rasika A RA Wilson Alexander F AF

BMC genetics 20051230

The beta 2 electroencephalogram (EEG) phenotype is used as a quantitative measure related to alcoholism, and evidence of linkage and association has previously been reported in the Collaborative Study on the Genetics of Alcoholism data. In this study, associations between the beta 2 EEG phenotype and single nucleotide polymorphisms from whole-genome Illumina and Affymetrix panels were investigated with the regression of offspring on mid-parent method to identify significant genetic effects and t ...[more]

PMID: 16451668

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Project description:BackgroundParent-offspring (PO) regression is a central tool to determine the heritability of phenotypic traits; i.e., the relative extent to which those traits are controlled by genetic factors. The applicability of PO regression to viral traits is unclear because the direction of viral transmission-who is the donor (parent) and who is the recipient (offspring)-is typically unknown and viral phylogenies are sparsely sampled.MethodsWe assessed the applicability of PO regression in a realistic setting using Ornstein-Uhlenbeck simulated data on phylogenies built from 11,442 Swiss HIV Cohort Study (SHCS) partial pol sequences and set-point viral load (SPVL) data from 3293 patients.ResultsWe found that the misidentification of donor and recipient plays a minor role in estimating heritability and showed that sparse sampling does not influence the mean heritability estimated by PO regression. A mixed-effect model approach yielded the same heritability as PO regression but could be extended to clusters of size greater than 2 and allowed for the correction of confounding effects. Finally, we used both methods to estimate SPVL heritability in the SHCS. We employed a wide range of transmission pair criteria to measure heritability and found a strong dependence of the heritability estimates to these criteria. For the most conservative genetic distance criteria, for which heritability estimates are conceptually expected to be closest to true heritability, we found estimates ranging from 32 to 46% across different bootstrap criteria. For less conservative distance criteria, we found estimates ranging down to 8%. All estimates did not change substantially after adjusting for host-demographic factors in the mixed-effect model (±2%).ConclusionsFor conservative transmission pair criteria, both PO regression and mixed-effect models are flexible and robust tools to estimate the contribution of viral genetic effects to viral traits under real-world settings. Overall, we find a strong effect of viral genetics on SPVL that is not confounded by host demographics.

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Project description:Quantitative genetic parameters are nowadays more frequently estimated with restricted maximum likelihood using the 'animal model' than with traditional methods such as parent-offspring regressions. These methods have however rarely been evaluated using equivalent data sets. We compare heritabilities and genetic correlations from animal model and parent-offspring analyses, respectively, using data on eight morphological traits in the great reed warbler (Acrocephalus arundinaceus). Animal models were run using either mean trait values or individual repeated measurements to be able to separate between effects of including more extended pedigree information and effects of replicated sampling from the same individuals. We show that the inclusion of more pedigree information by the use of mean traits animal models had limited effect on the standard error and magnitude of heritabilities. In contrast, the use of repeated measures animal model generally had a positive effect on the sampling accuracy and resulted in lower heritabilities; the latter due to lower additive variance and higher phenotypic variance. For most trait combinations, both animal model methods gave genetic correlations that were lower than the parent-offspring estimates, whereas the standard errors were lower only for the mean traits animal model. We conclude that differences in heritabilities between the animal model and parent-offspring regressions were mostly due to the inclusion of individual replicates to the animal model rather than the inclusion of more extended pedigree information. Genetic correlations were, on the other hand, primarily affected by the inclusion of more pedigree information. This study is to our knowledge the most comprehensive empirical evaluation of the performance of the animal model in relation to parent-offspring regressions in a wild population. Our conclusions should be valuable for reconciliation of data obtained in earlier studies as well as for future meta-analyses utilizing estimates from both traditional methods and the animal model.

Project description:Importance:Previous 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. Objective:To examine associations of parent and offspring religiosity with suicide ideation and attempts in offspring. Design, Setting, and Participants:The 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 Measures:Parents' 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. Results:Of 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 Relevance:In 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.

Dataset Information

Application of the regression of offspring on mid-parent method to detect associations between single-nucleotide polymorphisms and the beta 2 electroencephalogram phenotype in the COGA data.

Publications

Application of the regression of offspring on mid-parent method to detect associations between single-nucleotide polymorphisms and the beta 2 electroencephalogram phenotype in the COGA data.

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