Intermediate phenotypes and genetic mechanisms of psychiatric disorders

2006 ◽  
Vol 7 (10) ◽  
pp. 818-827 ◽  
Author(s):  
Andreas Meyer-Lindenberg ◽  
Daniel R. Weinberger
Keyword(s):  
Psychiatric Disorders ◽  
Intermediate Phenotypes ◽  
Genetic Mechanisms

scholarly journals Assessing the Causal Effects of Human Serum Metabolites on 5 Major Psychiatric Disorders

2020 ◽  
Vol 46 (4) ◽  
pp. 804-813 ◽  
Author(s):  
Jian Yang ◽  
Bin Yan ◽  
Binbin Zhao ◽  
Yajuan Fan ◽  
Xiaoyan He ◽  
...  
Keyword(s):  
Human Serum ◽  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Association Studies ◽  
Autism Spectrum ◽  
Causal Effects ◽  
Human Diseases ◽  
Genome Wide Association Studies ◽  
Serum Metabolites ◽  
Intermediate Phenotypes

Abstract Psychiatric disorders are the leading cause of disability worldwide while the pathogenesis remains unclear. Genome-wide association studies (GWASs) have made great achievements in detecting disease-related genetic variants. However, functional information on the underlying biological processes is often lacking. Current reports propose the use of metabolic traits as functional intermediate phenotypes (the so-called genetically determined metabotypes or GDMs) to reveal the biological mechanisms of genetics in human diseases. Here we conducted a two-sample Mendelian randomization analysis that uses GDMs to assess the causal effects of 486 human serum metabolites on 5 major psychiatric disorders, which respectively were schizophrenia (SCZ), major depression (MDD), bipolar disorder (BIP), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Using genetic variants as proxies, our study has identified 137 metabolites linked to the risk of psychiatric disorders, including 2-methoxyacetaminophen sulfate, which affects SCZ (P = 1.7 × 10–5) and 1-docosahexaenoylglycerophosphocholine, which affects ADHD (P = 5.6 × 10–5). Fourteen significant metabolic pathways involved in the 5 psychiatric disorders assessed were also detected, such as glycine, serine, and threonine metabolism for SCZ (P = .0238), Aminoacyl-tRNA biosynthesis for both MDD (P = .0144) and ADHD (P = .0029). Our study provided novel insights into integrating metabolomics with genomics in order to understand the mechanisms underlying the pathogenesis of human diseases.

Transgressive segregation and maternal genetic effects of non–target site fluazifop-P-butyl tolerance in Zoysia spp.

Weed Science ◽  
2019 ◽  
Vol 67 (05) ◽  
pp. 504-509
Author(s):  
Wenwen Liu ◽  
Kevin E. Kenworthy ◽  
Gregory E. MacDonald ◽  
J. Bryan Unruh ◽  
Laurie E. Trenholm ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Breeding Population ◽  
Transgressive Segregation ◽  
Target Site ◽  
Multiple Traits ◽  
Intermediate Phenotypes ◽  
Wide Range ◽  
Genetic Mechanisms ◽  
Tolerant Line ◽  
Biomass Reduction

AbstractZoysia germplasm exhibit different levels of sensitivity to fluazifop-P-butyl, but the genetic factors responsible for such differences are unknown. Segregation patterns of the fluazifop-P-butyl tolerance trait were studied under greenhouse conditions. In total, 244 F1 lines were generated from multiple crosses between the tolerant line 5337-2 (non–target site tolerance) and three more-sensitive lines (123, 252, and 5330-23). Progeny segregation showed that fluazifop-P-butyl tolerance within zoysiagrass (Zoysia spp.) is expressed as a quantitative trait with a wide range of intermediate phenotypes between parental phenotypes. Transgressive segregation was extensive and largely favored susceptibility in most families, but was especially evident for 5337-2 × 123 and 5337-2 × 5330-23. The segregation patterns for biomass reduction and percent injury were different within reciprocal crosses and among three different family crosses. Reciprocal effects were observed in growth reduction for 5337-2 × 5330-23, in percent injury at 3 wk after the treatment (WAT), and for 5337-2 × 252 at 6 WAT. This indicated that fluazifop-P-butyl tolerance was not completely controlled by nuclear genetic factors in 5337-2 and maternal/cytoplasmic inheritance was also partially responsible. These results suggested that fluazifop-P-butyl tolerance may be attributed to multiple genetic mechanisms, which could present a challenge for future breeding efforts because of the difficulty of fixing multiple traits within a breeding population.

scholarly journals Intermediate phenotypes in psychiatric disorders

2011 ◽  
Vol 21 (3) ◽  
pp. 340-348 ◽  
Author(s):  
Roberta Rasetti ◽  
Daniel R Weinberger
Keyword(s):  
Psychiatric Disorders ◽  
Intermediate Phenotypes

scholarly journals Persistence of a Geographically-Stable Hybrid Zone in Puerto Rican Dwarf Geckos

2019 ◽  
Vol 110 (5) ◽  
pp. 523-534 ◽  
Author(s):  
Brendan J Pinto ◽  
James Titus-McQuillan ◽  
Juan D Daza ◽  
Tony Gamble
Keyword(s):  
Reproductive Isolation ◽  
Hybrid Zone ◽  
Sequence Data ◽  
Strong Support ◽  
Climatic Variables ◽  
Putative Hybrid ◽  
Hybrid Zones ◽  
Intermediate Phenotypes ◽  
Genetic Mechanisms ◽  
Stable Hybrid

Abstract Determining the mechanisms that create and maintain biodiversity is a central question in ecology and evolution. Speciation is the process that creates biodiversity. Speciation is mediated by incompatibilities that lead to reproductive isolation between divergent populations and these incompatibilities can be observed in hybrid zones. Gecko lizards are a speciose clade possessing an impressive diversity of behavioral and morphological traits. In geckos, however, our understanding of the speciation process is negligible. To address this gap, we used genetic sequence data (both mitochondrial and nuclear markers) to revisit a putative hybrid zone between Sphaerodactylus nicholsi and Sphaerodactylus townsendi in Puerto Rico, initially described in 1984. First, we addressed discrepancies in the literature on the validity of both species. Second, we sampled a 10-km-wide transect across the putative hybrid zone and tested explicit predictions about its dynamics using cline models. Third, we investigated potential causes for the hybrid zone using species distribution modeling and simulations; namely, whether unique climatic variables within the hybrid zone might elicit selection for intermediate phenotypes. We find strong support for the species-level status of each species and no evidence of movement, or unique climatic variables near the hybrid zone. We suggest that this narrow hybrid zone is geographically stable and is maintained by a combination of dispersal and selection. Thus, this work has identified an extant model system within geckos that that can be used for future investigations detailing genetic mechanisms of reproductive isolation in an understudied vertebrate group.

Methods and theoretical approaches

2019 ◽  
pp. 77-96
Author(s):  
Celine L St Pierre ◽  
Kayvon Sharif ◽  
Emily Funsten ◽  
Abraham A Palmer ◽  
Clarissa C Parker
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Human Studies ◽  
Rodent Models ◽  
Appropriate Use ◽  
Risk Genes ◽  
Intermediate Phenotypes ◽  
Theoretical Approaches ◽  
Anxiety Depression ◽  
Dynamic Interplay

Anxiety, depression, and stress-related disorders are complex neurobehavioral diseases with a partially heritable genetic basis. This chapter explores how the appropriate use of rodent models can illuminate the neurobiological underpinnings of these disorders. Because these psychiatric disorders are uniquely human, rodent models typically model individual components rather than trying to recapitulate the disease itself. This chapter considers how both intermediate phenotypes and rodent models fit into this framework. Integrating these two concepts can be bidirectional: studying intermediate phenotypes in rodent models may lead to identifying risk genes that are present in humans, or human studies may uncover genetic variants linked to intermediate phenotypes and subsequent experiments in rodents may be employed to examine the causal mechanisms. This dynamic interplay is explored throughout the chapter.

Shared genetic etiology between anxiety disorders and psychiatric and related intermediate phenotypes

2019 ◽  
Vol 50 (4) ◽  
pp. 692-704 ◽  
Author(s):  
Kazutaka Ohi ◽  
Takeshi Otowa ◽  
Mihoko Shimada ◽  
Tsukasa Sasaki ◽  
Hisashi Tanii
Keyword(s):  
Anxiety Disorders ◽  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Large Scale ◽  
Genetic Correlations ◽  
Well Being ◽  
Subjective Well Being ◽  
Intermediate Phenotypes ◽  
Genome Wide ◽  
Common Genetic Variants

AbstractBackgroundPsychiatric disorders and related intermediate phenotypes are highly heritable and have a complex, overlapping polygenic architecture. A large-scale genome-wide association study (GWAS) of anxiety disorders identified genetic variants that are significant on a genome-wide. The current study investigated the genetic etiological overlaps between anxiety disorders and frequently cooccurring psychiatric disorders and intermediate phenotypes.MethodsUsing case–control and factor score models, we investigated the genetic correlations of anxiety disorders with eight psychiatric disorders and intermediate phenotypes [the volumes of seven subcortical brain regions, childhood cognition, general cognitive ability and personality traits (subjective well-being, loneliness, neuroticism and extraversion)] from large-scale GWASs (n= 7556–298 420) by linkage disequilibrium score regression.ResultsAmong psychiatric disorders, the risk of anxiety disorders was positively genetically correlated with the risks of major depressive disorder (MDD) (rg± standard error = 0.83 ± 0.16,p= 1.97 × 10−7), schizophrenia (SCZ) (0.28 ± 0.09,p= 1.10 × 10−3) and attention-deficit/hyperactivity disorder (ADHD) (0.34 ± 0.13,p= 8.40 × 10−3). Among intermediate phenotypes, significant genetic correlations existed between the risk of anxiety disorders and neuroticism (0.81 ± 0.17,p= 1.30 × 10−6), subjective well-being (−0.73 ± 0.18,p= 4.89 × 10−5), general cognitive ability (−0.23 ± 0.08,p= 4.70 × 10−3) and putamen volume (−0.50 ± 0.18,p= 5.00 × 10−3). No other significant genetic correlations between anxiety disorders and psychiatric or intermediate phenotypes were observed (p> 0.05). The case–control model yielded stronger genetic effect sizes than the factor score model.ConclusionsOur findings suggest that common genetic variants underlying the risk of anxiety disorders contribute to elevated risks of MDD, SCZ, ADHD and neuroticism and reduced quality of life, putamen volume and cognitive performance. We suggest that the comorbidity of anxiety disorders is partly explained by common genetic variants.

Biomarkers in psychiatry: a clinician’s viewpoint

2020 ◽  
Vol 135 (1) ◽  
pp. 23-27
Author(s):  
Tariq Mahmood
Keyword(s):  
Clinical Practice ◽  
Psychiatric Disorders ◽  
Psychiatric Patients ◽  
New Drugs ◽  
Psychiatric Diagnoses ◽  
Current Clinical Practice ◽  
Cross Sectional ◽  
Intermediate Phenotypes ◽  
Individualized Approach ◽  
New Treatments

Abstract Introduction The dearth of biomarkers limits the precision of our research into pathogenesis of psychiatric disorders and has slowed down the development of new drugs. In clinical practice, it undermines the validity of psychiatric diagnoses and hampers the delivery of personalized treatment. Sources of data The data quoted in this paper are gathered from a range of sources encompassing scientific and journalistic both in print and electronic. Areas of agreement Availability of clinically useful biomarkers will improve the prognosis and outcome of psychiatric patients by helping in early diagnosis and delivery of individualized treatment. Areas of controversy The cross-sectional and longitudinal observation of psychopathology is the bedrock of current clinical practice. Are psychiatric biomarkers advanced enough to supplant it? Growing points The need for biomarkers of psychiatric disorders has become more acute with the advent of new treatments which require precision and an individualized approach. Areas timely for developing research Identification and deployment of intermediate phenotypes in classification, research and clinical practice of psychiatry.

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