Nevin Manimala

Stat Med. 2022 May 18. doi: 10.1002/sim.9440. Online ahead of print.

ABSTRACT

Correlated phenotypes often share common genetic determinants. Thus, a multi-trait analysis can potentially increase association power and help in understanding pleiotropic effect. When multiple traits are jointly measured over time, the correlation information between multivariate longitudinal responses can help to gain power in association analysis, and the longitudinal traits can provide insights on the dynamic gene effect over time. In this work, we propose a multivariate partially linear varying coefficients model to identify genetic variants with their effects potentially modified by environmental factors. We derive a testing framework to jointly test the association of genetic factors and illustrated with a bivariate phenotypic trait, while taking the time varying genetic effects into account. We extend the quadratic inference functions to deal with the longitudinal correlations and used penalized splines for the approximation of nonparametric coefficient functions. Theoretical results such as consistency and asymptotic normality of the estimates are established. The performance of the testing procedure is evaluated through Monte Carlo simulation studies. The utility of the method is demonstrated with a real data set from the Twin Study of Hormones and Behavior across the menstrual cycle project, in which single nucleotide polymorphisms associated with emotional eating behavior are identified.

PMID:35582816 | DOI:10.1002/sim.9440

Stat Med. 2022 May 18. doi: 10.1002/sim.9408. Online ahead of print.

ABSTRACT

To strengthen inferences meta-analyses are commonly used to summarize information from a set of independent studies. In some cases, though, the data may not satisfy the assumptions underlying the meta-analysis. Using three Bayesian methods that have a more general structure than the common meta-analytic ones, we can show the extent and nature of the pooling that is justified statistically. In this article, we reanalyze data from several reviews whose objective is to make inference about the COVID-19 asymptomatic infection rate. When it is unlikely that all of the true effect sizes come from a single source researchers should be cautious about pooling the data from all of the studies. Our findings and methodology are applicable to other COVID-19 outcome variables, and more generally.

PMID:35582808 | DOI:10.1002/sim.9408

Proc Biol Sci. 2022 May 25;289(1975):20212535. doi: 10.1098/rspb.2021.2535. Epub 2022 May 18.

ABSTRACT

A clade’s evolutionary history is shaped, in part, by geographical range expansion, sweepstakes dispersal and local extinction. A rigorous understanding of historical biogeography may therefore yield insights into macroevolutionary dynamics such as adaptive radiation. Modern historical biogeographic analyses typically fit statistical models to molecular phylogenies, but it remains unclear whether extant species provide sufficient signal or if well-sampled phylogenies of extinct and extant taxa are necessary to produce meaningful estimates of past ranges. We investigated the historical biogeography of Primates and their euarchontan relatives using a novel meta-analytical phylogeny of over 900 extant (n= 419) and extinct (n = 483) species spanning their entire evolutionary history. Ancestral range estimates for young nodes were largely congruent with those derived from molecular phylogeny. However, node age exerts a significant effect on ancestral range estimate congruence, and the probability of congruent inference dropped below 0.5 for nodes older than the late Eocene, corresponding to the origins of higher-level clades. Discordance was not observed in analyses of extinct taxa alone. Fossils are essential for robust ancestral range inference and biogeographic analyses of extant clades originating in the deep past should be viewed with scepticism without them.

PMID:35582793 | DOI:10.1098/rspb.2021.2535

Am J Psychiatry. 2022 May 18:appiajp20081180. doi: 10.1176/appi.ajp.20081180. Online ahead of print.

ABSTRACT

OBJECTIVE: Research in adolescent depression has found aberrant intrinsic functional connectivity (iFC) among the ventral striatum (VS) and several brain regions implicated in reward processing. The present study probes this question by taking advantage of the availability of data from a large youth cohort, the IMAGEN Consortium.

METHODS: iFC data from 303 adolescents (48% of them female) were used to examine associations of VS connectivity at baseline (at age 14) with depressive disorders at baseline and at 2-year (N=250) and 4-year (N=219) follow-ups. Eleven regions of interest, key nodes of the reward system, were used to probe the reward network and calculate the connectivity strength of the VS within this network (VS connectivity_rw). The main analyses assessed associations of VS connectivity_rw with depressive disorders, anhedonia, and low mood using logistic regression. Autoregressive models accounting for carryover effects over time were conducted to further evaluate these brain-behavior associations.

RESULTS: Higher right VS connectivity_rw was associated with higher probability of depressive disorders at baseline (odds ratio=2.65, 95% CI=1.40, 5.05). This finding was confirmed in the autoregressive model, adjusting for carryover effects of the depressive disorders across the three time points. VS connectivity_rw was not predictive of depressive disorders at follow-up assessments. Longitudinal associations between VS connectivity_rw and anhedonia emerged in the structural equation model: left VS connectivity_rw was associated with anhedonia at 2 years (odds ratio=2.20, 95% CI=1.54, 3.14), and right VS connectivity_rw was linked to anhedonia at 4 years (odds ratio=1.87, 95% CI=1.09, 3.21). VS connectivity_rw did not predict low mood at any time point in the structural equation model.

CONCLUSIONS: The connectivity strength of the VS within the reward network showed distinct patterns of association with depressive disorders and anhedonia from mid to late adolescence, suggesting that the role of this circuitry in depression changes with age. This study replicates, in an independent sample, the association between the VS and depression previously reported in younger adolescents. The findings suggest a role of VS connectivity_rw in anhedonia but not in low mood.

PMID:35582783 | DOI:10.1176/appi.ajp.20081180