scholarly journals Parent of Origin Effects on Quantitative Phenotypes in a Founder Population

2017 ◽  
Author(s):  
Sahar V. Mozaffari ◽  
Jeanne M. DeCara ◽  
Sanjiv J. Shah ◽  
Roberto M. Lang ◽  
Dan L. Nicolae ◽  
...  
Keyword(s):  
Risk Factors ◽  
Single Parent ◽  
Parental Origin ◽  
Parental Effects ◽  
Sequence Variants ◽  
Clinical Effects ◽  
Founder Population ◽  
Parent Of Origin ◽  
Origin Effects ◽  
The Impact

ABSTRACTThe impact of the parental origin of associated alleles in GWAS has been largely ignored. Yet sequence variants could affect traits differently depending on whether they are inherited from the mother or the father. To explore this possibility, we studied 21 quantitative phenotypes in a large Hutterite pedigree. We first identified variants with significant single parent (maternal-only or paternal-only) effects, and then used a novel statistical model to identify variants with opposite parental effects. Overall, we identified parent of origin effects (POEs) on 11 phenotypes, most of which are risk factors for cardiovascular disease. Many of the loci with POEs have features of imprinted regions and many of the variants with POE are associated with the expression of nearby genes. Overall, our results indicate that POEs, which are often opposite in direction, are relatively common in humans, have potentially important clinical effects, and will be missed in traditional GWAS.

A parsimonious model for an analysis of parent-of-origin effects on beef traits in dual-purpose Simmental

2017 ◽  
Vol 8 (s1) ◽  
pp. s76-s78 ◽  
Author(s):  
I. Blunk ◽  
M. Mayer ◽  
H. Hamann ◽  
N. Reinsch
Keyword(s):  
Large Data ◽  
Equation System ◽  
Parental Origin ◽  
Data Sets ◽  
Linear Version ◽  
Equivalent Version ◽  
Parent Of Origin ◽  
Origin Effects ◽  
Parsimonious Model ◽  
Fat Score

Genomic imprinting is a term applied to an epigenetic phenomenon where alleles are fully or partially inactivated depending on their parental origin. The relevance of this kind of parent-of-origin effects (POEs) for agriculturally important traits is widely known. A model (imprinting model) with a transmitting ability (TA) as sire and a TA as dam has been proposed that provides an estimate of the imprinting variance, whether the allelic inactivation is maternal, paternal, full or partial. Although the model can be used in a reduced version, large data sets still prevent the imprinting variance from being estimated. To further reduce the size of the equation system, we developed a parsimonious imprinting model with genetic effects for male ancestors only, as the TA as dam is replaced by her father’s TA. This parsimonious model was applied to 1 366 160 Simmental fattening bulls with slaughter data available on killing out percentage, net BW gain, EUROP class and fat score in a linear and generalised linear version. The pedigrees contained up to 2 637 761 ancestors. Proportion of the total genetic variance attributed to POEs ranged between 8.6% and 17.0%. On average, the maternal gamete accounted for the greater proportion of the imprinting variance. An equivalent version of the parsimonious model facilitated the estimation of POEs with reliabilities ranging between zero and 0.97.

scholarly journals Parent-of-origin effects on cardiac response to pressure overload in mice

2009 ◽  
Vol 297 (3) ◽  
pp. H1003-H1009 ◽  
Author(s):  
Cordelia J. Barrick ◽  
Anping Dong ◽  
Rebekah Waikel ◽  
Drew Corn ◽  
Fanmuyi Yang ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Pressure Overload ◽  
Inbred Strains ◽  
Mendelian Inheritance ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Heart Weight ◽  
Parental Origin ◽  
Parent Of Origin ◽  
Origin Effects

Left ventricular (LV) hypertrophy (LVH) is an independent risk factor for cardiovascular mortality and is commonly caused by hypertension. In rodents, transverse aortic constriction (TAC) is a model regularly employed in mechanistic studies of the response of the LV to pressure overload. We previously reported that inbred strains of male mice manifest different cardiac responses to TAC, with C57BL/6J (B6) developing LV dilatation and impaired contractility and 129S1/SvImJ (129) males displaying concentric LVH. In the present study, we investigated sex and parent-of-origin effects on the response to TAC by comparing cardiac function, organ weights, expression of cardiac hypertrophy markers, and histology in female B6 and female 129 mice and in F1 progeny of reciprocal crosses between B6 and 129 mice (B6129F1 and 129B6F1). Five weeks after TAC, heart weight increased to the greatest extent in 129B6F1 mice and the least extent in 129 and B6129F1 mice. Female 129B6F1 and B6 mice were relatively protected from the increase in heart weight that occurs in their male counterparts with pressure overload. The response to TAC in 129 consomic mice bearing the B6 Y chromosome resembled that of 129 rather than 129B6F1 mice, indicating that the B6 Y chromosome does not account for the differences in the reciprocal cross. Our results suggest that susceptibility to LVH is more complex than simple Mendelian inheritance and that parental origin effects strongly impact the LV response to TAC in these commonly used inbred strains.

scholarly journals A statistical test for detecting parent-of-origin effects when parental information is missing

2017 ◽  
Vol 16 (4) ◽  
Author(s):  
Chiara Sacco ◽  
Cinzia Viroli ◽  
Mario Falchi
Keyword(s):  
Study Data ◽  
Epigenetic Mechanism ◽  
Parental Origin ◽  
Reference Allele ◽  
Parental Effect ◽  
Genome Wide ◽  
Parent Of Origin ◽  
Related Individuals ◽  
Origin Effects ◽  
Parental Information

AbstractGenomic imprinting is an epigenetic mechanism that leads to differential contributions of maternal and paternal alleles to offspring gene expression in a parent-of-origin manner. We propose a novel test for detecting the parent-of-origin effects (POEs) in genome wide genotype data from related individuals (twins) when the parental origin cannot be inferred. The proposed method exploits a finite mixture of linear mixed models: the key idea is that in the case of POEs the population can be clustered in two different groups in which the reference allele is inherited by a different parent. A further advantage of this approach is the possibility to obtain an estimation of parental effect when the parental information is missing. We will also show that the approach is flexible enough to be applicable to the general scenario of independent data. The performance of the proposed test is evaluated through a wide simulation study. The method is finally applied to known imprinted genes of the MuTHER twin study data.

scholarly journals Lipid-Associated Variants near ANGPTL3 and LPL Show Parent-of-Origin Specific Effects on Blood Lipid Levels and Obesity

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 91
Author(s):  
Anna Lessmark ◽  
Gad Hatem ◽  
Györgyi Kovacs ◽  
Marta Vitai ◽  
Emma Ahlqvist ◽  
...  
Keyword(s):  
Complex Traits ◽  
Plasma Lipid ◽  
Blood Lipid ◽  
Strong Relationship ◽  
Parental Origin ◽  
Parental Effects ◽  
Lipid Levels ◽  
Specific Effects ◽  
Parent Of Origin ◽  
Blood Lipid Levels

Parent-of-origin effects (POE) and sex-specific parental effects have been reported for plasma lipid levels, and a strong relationship exists between dyslipidemia and obesity. We aim to explore whether genetic variants previously reported to have an association to lipid traits also show POE on blood lipid levels and obesity. Families from the Botnia cohort and the Hungarian Transdanubian Biobank (HTB) were genotyped for 12 SNPs, parental origin of alleles were inferred, and generalized estimating equations were modeled to assess parental-specific associations with lipid traits and obesity. POE were observed for the variants at the TMEM57, DOCK7/ANGPTL3, LPL, and APOA on lipid traits, the latter replicated in HTB. Sex-specific parental effects were also observed; variants at ANGPTL3/DOCK7 showed POE on lipid traits and obesity in daughters only, while those at LPL and TMEM57 showed POE on lipid traits in sons. Variants at LPL and DOCK7/ANGPTL3 showed POE on obesity-related traits in Botnia and HTB, and POE effects on obesity were seen to a higher degree in daughters. This highlights the need to include analysis of POEs in genetic studies of complex traits.

scholarly journals Genome-Wide Scan for Parent-of-Origin Effects in a sub-Saharan African Cohort With Nonsyndromic Cleft Lip and/or Cleft Palate (CL/P)

2021 ◽  
pp. 105566562110363
Author(s):  
Lord J. J. Gowans ◽  
Carissa L. Comnick ◽  
Peter A. Mossey ◽  
Mekonen A. Eshete ◽  
Wasiu L. Adeyemo ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Association Studies ◽  
African Ancestry ◽  
Parental Origin ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
A Genome ◽  
Parent Of Origin ◽  
Origin Effects

Objective Nonsyndromic cleft lip and/or cleft palate (NSCL/P) have multifactorial etiology where genetic factors, gene–environment interactions, stochastic factors, gene–gene interactions, and parent-of-origin effects (POEs) play cardinal roles. POEs arise when the parental origin of alleles differentially impacts the phenotype of the offspring. The aim of this study was to identify POEs that can increase risk for NSCL/P in humans using a genome-wide dataset. Methods The samples (174 case-parent trios from Ghana, Ethiopia, and Nigeria) included in this study were from the African only genome wide association studies (GWAS) that was published in 2019. Genotyping of individual DNA using over 2 million multiethnic and African ancestry-specific single-nucleotide polymorphisms from the Illumina Multi-Ethnic Genotyping Array v2 15070954 A2 (genome build GRCh37/hg19) was done at the Center for Inherited Diseases Research. After quality control checks, PLINK was employed to carry out POE analysis employing the pooled subphenotypes of NSCL/P. Results We observed possible hints of POEs at a cluster of genes at a 1 mega base pair window at the major histocompatibility complex class 1 locus on chromosome 6, as well as at other loci encompassing candidate genes such as ASB18, ANKEF1, AGAP1, GABRD, HHAT, CCT7, DNMT3A, EPHA7, FOXO3, lncRNAs, microRNA, antisense RNAs, ZNRD1, ZFAT, and ZBTB16. Conclusion Findings from our study suggest that some loci may increase the risk for NSCL/P through POEs. Additional studies are required to confirm these suggestive loci in NSCL/P etiology.

scholarly journals Coping-Style Behavior Identified by a Survey of Parent-of-Origin Effects in the Rat

2018 ◽  
Author(s):  
Carme Mont ◽  
Polinka Hernandez Pilego ◽  
Toni Cañete ◽  
Ignasi Oliveras ◽  
Cristóbal Río-Álamos ◽  
...  
Keyword(s):  
Complex Traits ◽  
Coping Style ◽  
Additive Genetic Variance ◽  
Shared Environment ◽  
Parental Origin ◽  
Impulsive Behavior ◽  
Develop Theory ◽  
Parent Of Origin ◽  
Origin Effects ◽  
F1 Cross

AbstractWe develop theory, based on earlier work, to partition heritability into a component due to a combination of parent of origin, maternal, paternal and shared environment, and another component that estimates classical additive genetic variance. We then investigate the effects on heritability of the parental origin of alleles in outbred heterogeneous stock rats across 199 complex traits. Parent-of-origin-like heritability was on average 2.7-fold larger than classical additive heritability. Among the phenotypes with the most enhanced parent-of-origin heritability were 10 coping style behaviors, with average 3.2-fold heritability enrichment. To confirm these findings on coping behaviour, and to eliminate the possibility that the parent of origin effects are due to confounding with shared environment, we performed a reciprocal F1 cross between the behaviourally divergent RHA and RLA rat strains. We observed parent-of-origin effects on F1 rat anxiety/coping-related behavior in the Elevated Zero Maze test. Our results are the first to assess genetic parent-of-origin effects in rats, and confirm earlier findings in mice that such effects influence mammalian coping and impulsive behavior.

Analysis of parent of origin effects in Sorbs using long range phasing algorithms

2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
X Liu ◽  
M Scholz ◽  
A Tönjes ◽  
M Stumvoll ◽  
PF Stadler ◽  
...  
Keyword(s):  
Long Range ◽  
Parent Of Origin ◽  
Origin Effects

Stress, Cortisol and Suicide Risk

2019 ◽  
Author(s):  
Daryl Brian O'Connor
Keyword(s):  
Risk Factors ◽  
Suicidal Behavior ◽  
Suicide Risk ◽  
Stressful Events ◽  
Additional Risk ◽  
Global Health Issue ◽  
History Of ◽  
Hpa Axis Activity ◽  
The Impact

Suicide is a global health issue accounting for at least 800,000 deaths per annum. Numerous models have been proposed that differ in their emphasis on the role of psychological, social, psychiatric and neurobiological factors in explaining suicide risk. Central to many models is a stress-diathesis component which states that suicidal behavior is the result of an interaction between acutely stressful events and a susceptibility to suicidal behavior (a diathesis). This article presents an overview of studies that demonstrate that stress and dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, are important additional risk factors for suicide. Evidence for other putative stress-related suicide risk factors including childhood trauma, impaired executive function, impulsivity and disrupted sleep are considered together with the impact of family history of suicide, perinatal and epigenetic influences on suicide risk.

Stress, anxiety, depression and burnout in frontline health care workers during COVID-19 pandemic: a brief systematic review and new data from Russia

2021 ◽  
Author(s):  
Ekaterina Mosolova ◽  
Dmitry Sosin ◽  
Sergey Mosolov
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Female Gender ◽  
Assessment Tools ◽  
Care Workers ◽  
Younger Age ◽  
Wide Range ◽  
Associated Risk Factors ◽  
Anxiety Depression ◽  
The Impact

During the COVID-19 pandemic, healthcare workers (HCWs) have been subject to increased workload while also exposed to many psychosocial stressors. In a systematic review we analyze the impact that the pandemic has had on HCWs mental state and associated risk factors. Most studies reported high levels of depression and anxiety among HCWs worldwide, however, due to a wide range of assessment tools, cut-off scores, and number of frontline participants in the studies, results were difficult to compare. Our study is based on two online surveys of 2195 HCWs from different regions of Russia during spring and autumn epidemic outbreaks revealed the rates of anxiety, stress, depression, emotional exhaustion and depersonalization and perceived stress as 32.3%, 31.1%, 45.5%, 74.2%, 37.7% ,67.8%, respectively. Moreover, 2.4% of HCWs reported suicidal thoughts. The most common risk factors include: female gender, nurse as an occupation, younger age, working for over 6 months, chronic diseases, smoking, high working demands, lack of personal protective equipment, low salary, lack of social support, isolation from families, the fear of relatives getting infected. These results demonstrate the need for urgent supportive programs for HCWs fighting COVID-19 that fall into higher risk factors groups.

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