scholarly journals The genetic architecture of the human thalamus and its overlap with ten common brain disorders

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Torbjørn Elvsåshagen ◽  
Alexey Shadrin ◽  
Oleksandr Frei ◽  
Dennis van der Meer ◽  
Shahram Bahrami ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Sign Test ◽  
Brain Disorders ◽  
Nucleotide Polymorphisms ◽  
Thalamic Nuclei ◽  
Genetic Loci ◽  
Single Nucleotide ◽  
Brain Scans ◽  
Discovery Sample ◽  
Human Thalamus

AbstractThe thalamus is a vital communication hub in the center of the brain and consists of distinct nuclei critical for consciousness and higher-order cortical functions. Structural and functional thalamic alterations are involved in the pathogenesis of common brain disorders, yet the genetic architecture of the thalamus remains largely unknown. Here, using brain scans and genotype data from 30,114 individuals, we identify 55 lead single nucleotide polymorphisms (SNPs) within 42 genetic loci and 391 genes associated with volumes of the thalamus and its nuclei. In an independent validation sample (n = 5173) 53 out of the 55 lead SNPs of the discovery sample show the same effect direction (sign test, P = 8.6e-14). We map the genetic relationship between thalamic nuclei and 180 cerebral cortical areas and find overlapping genetic architectures consistent with thalamocortical connectivity. Pleiotropy analyses between thalamic volumes and ten psychiatric and neurological disorders reveal shared variants for all disorders. Together, these analyses identify genetic loci linked to thalamic nuclei and substantiate the emerging view of the thalamus having central roles in cortical functioning and common brain disorders.

scholarly journals Genome-wide association analysis of the human thalamus identifies novel genomic loci and reveals genetic overlap with distinct cortical regions and ten brain disorders

2020 ◽  
Author(s):  
Torbjorn Elvsashagen ◽  
Alexey A Shadrin ◽  
Oleksandr Frei ◽  
Dennis van der Meer ◽  
Shahram Bahrami ◽  
...  
Keyword(s):  
Sign Test ◽  
Brain Disorders ◽  
Thalamic Nuclei ◽  
Genetic Loci ◽  
Brain Scans ◽  
Human Thalamus ◽  
Genome Wide ◽  
Genetic Overlap ◽  
Cortical Regions ◽  
The Brain

The thalamus is a vital communication hub in the center of the brain and consists of distinct nuclei critical for consciousness and higher-order cortical functions. Structural and functional thalamic alterations are involved in the pathogenesis of common brain disorders, yet the genetic architecture of the thalamus remains largely unknown. Here, using brain scans and genotype data from 30,114 individuals, we identified 42 (41 novel) genetic loci and 392 genes associated with volumes of the thalamus and its nuclei. In an independent validation sample (n = 5,190) 96% of the loci showed the same effect direction (sign test, P = 8.6e-14). We mapped the genetic relationship between thalamic nuclei and 180 cerebral cortical areas and found overlapping genetic architectures consistent with thalamocortical connectivity. Pleiotropy analyses between thalamic volumes and ten psychiatric and neurological disorders revealed shared variants for all disorders. Together, these analyses identify the first genetic loci linked to thalamic nuclei and substantiate the emerging view of the thalamus having central roles in cortical functioning and common brain disorders.

scholarly journals Identification and Functional Annotation of Genes Related to Bone Stability in Laying Hens Using Random Forests

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 702
Author(s):  
Simon Jansen ◽  
Ulrich Baulain ◽  
Christin Habig ◽  
Faisal Ramzan ◽  
Jens Schauer ◽  
...  
Keyword(s):  
Random Forests ◽  
Metabolic Pathways ◽  
Genetic Architecture ◽  
Laying Hens ◽  
Enrichment Analysis ◽  
Nucleotide Polymorphisms ◽  
Mineral Density ◽  
Single Nucleotide ◽  
Economic Problems ◽  
Close Proximity

Skeletal disorders, including fractures and osteoporosis, in laying hens cause major welfare and economic problems. Although genetics have been shown to play a key role in bone integrity, little is yet known about the underlying genetic architecture of the traits. This study aimed to identify genes associated with bone breaking strength and bone mineral density of the tibiotarsus and the humerus in laying hens. Potentially informative single nucleotide polymorphisms (SNP) were identified using Random Forests classification. We then searched for genes known to be related to bone stability in close proximity to the SNPs and identified 16 potential candidates. Some of them had human orthologues. Based on our findings, we can support the assumption that multiple genes determine bone strength, with each of them having a rather small effect, as illustrated by our SNP effect estimates. Furthermore, the enrichment analysis showed that some of these candidates are involved in metabolic pathways critical for bone integrity. In conclusion, the identified candidates represent genes that may play a role in the bone integrity of chickens. Although further studies are needed to determine causality, the genes reported here are promising in terms of alleviating bone disorders in laying hens.

scholarly journals Genetics of complex traits: prediction of phenotype, identification of causal polymorphisms and genetic architecture

2016 ◽  
Vol 283 (1835) ◽  
pp. 20160569 ◽  
Author(s):  
M. E. Goddard ◽  
K. E. Kemper ◽  
I. M. MacLeod ◽  
A. J. Chamberlain ◽  
B. J. Hayes
Keyword(s):  
Complex Traits ◽  
Genetic Architecture ◽  
Quantitative Traits ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Crop Breeding ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Phenotype Identification

Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement.

scholarly journals Genome resequencing reveals demographic history and genetic architecture of seed salinity tolerance in Populus euphratica

2020 ◽  
Vol 71 (14) ◽  
pp. 4308-4320 ◽  
Author(s):  
Huixia Jia ◽  
Guangjian Liu ◽  
Jianbo Li ◽  
Jin Zhang ◽  
Pei Sun ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Salinity Tolerance ◽  
Genetic Architecture ◽  
Demographic History ◽  
Populus Euphratica ◽  
Tectonic Deformation ◽  
Nucleotide Polymorphisms ◽  
Genome Resequencing ◽  
Single Nucleotide ◽  
Climatic Fluctuations

Abstract Populus euphratica is a dominant tree species in desert riparian forests and possesses extraordinary adaptation to salinity stress. Exploration of its genomic variation and molecular underpinning of salinity tolerance is important for elucidating population evolution and identifying stress-related genes. Here, we identify approximately 3.15 million single nucleotide polymorphisms using whole-genome resequencing. The natural populations of P. euphratica in northwest China are divided into four distinct clades that exhibit strong geographical distribution patterns. Pleistocene climatic fluctuations and tectonic deformation jointly shaped the extant genetic patterns. A seed germination rate-based salinity tolerance index was used to evaluate seed salinity tolerance of P. euphratica and a genome-wide association study was implemented. A total of 38 single nucleotide polymorphisms were associated with seed salinity tolerance and were located within or near 82 genes. Expression profiles showed that most of these genes were regulated under salt stress, revealing the genetic complexity of seed salinity tolerance. Furthermore, DEAD-box ATP-dependent RNA helicase 57 and one undescribed gene (CCG029559) were demonstrated to improve the seed salinity tolerance in transgenic Arabidopsis. These results provide new insights into the demographic history and genetic architecture of seed salinity tolerance in desert poplar.

scholarly journals The combination of single nucleotide polymorphisms rs6720173 (ABCG5), rs3808607 (CYP7A1), and rs760241 (DHCR7) is associated with differing serum cholesterol responses to dairy consumption

2018 ◽  
Vol 43 (10) ◽  
pp. 1090-1093 ◽  
Author(s):  
Mohammad M.H. Abdullah ◽  
Peter K. Eck ◽  
Patrick Couture ◽  
Benoît Lamarche ◽  
Peter J.H. Jones
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Serum Cholesterol ◽  
Genetic Architecture ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Nucleotide Polymorphisms ◽  
Low Density Lipoprotein Cholesterol ◽  
Dietary Interventions ◽  
Single Nucleotide ◽  
Dairy Consumption

Existing evidence on the influence of genetic architecture on serum cholesterol responsiveness to dietary interventions focuses on individual single nucleotide polymorphisms and single nutrients. We associated the combination of ABCG5 rs6720173-C, CYP7A1 rs3808607-TT, and DHCR7 rs760241-GG genotypes with lower low-density lipoprotein cholesterol concentrations relative to the combination of rs6720173-GG, rs3808607-G, and rs760241-A genotypes (–0.37 ± 0.12 (n = 9) vs. +0.38 ± 0.14 mmol/L (n = 7), p = 0.0016) following a blended dairy (3 servings/day for 4 weeks) intervention.

scholarly journals Highly heritable and functionally relevant breed differences in dog behaviour

2019 ◽  
Vol 286 (1912) ◽  
pp. 20190716 ◽  
Author(s):  
Evan L. MacLean ◽  
Noah Snyder-Mackler ◽  
Bridgett M. vonHoldt ◽  
James A. Serpell
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Genetic Similarity ◽  
Genetic Architecture ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Biological Basis ◽  
Trait Variance ◽  
Breed Differences ◽  
The Brain ◽  
Shed Light

Variation across dog breeds presents a unique opportunity to investigate the evolution and biological basis of complex behavioural traits. We integrated behavioural data from more than 14 000 dogs from 101 breeds with breed-averaged genotypic data ( n = 5697 dogs) from over 100 000 loci in the dog genome. We found high levels of among-breed heritability for 14 behavioural traits (the proportion of trait variance attributable to genetic similarity among breeds). We next identified 131 single nucleotide polymorphisms associated with breed differences in behaviour, which were found in genes that are highly expressed in the brain and enriched for neurobiological functions and developmental processes, suggesting that they may be functionally associated with behavioural differences. Our results shed light on the heritability and genetic architecture of complex behavioural traits and identify dogs as a powerful model in which to address these questions.

scholarly journals Highly Heritable and Functionally Relevant Breed Differences in Dog Behavior

2019 ◽  
Author(s):  
Evan L MacLeant ◽  
Noah Snyder-Mackler ◽  
Bridgett M. vonHoldt ◽  
James A. Serpell
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Genetic Architecture ◽  
Genetic Relationships ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Biological Basis ◽  
Behavioral Traits ◽  
Breed Differences ◽  
The Brain ◽  
Insight Into

AbstractVariation across dog breeds presents a unique opportunity for investigating the evolution and biological basis of complex behavioral traits. We integrated behavioral data from more than 17,000 dogs from 101 breeds with breed-averaged genotypic data (N = 5,697 dogs) from over 100,000 loci in the dog genome. Across 14 traits, we found that breed differences in behavior are highly heritable, and that clustering of breeds based on behavior accurately recapitulates genetic relationships. We identify 131 single nucleotide polymorphisms associated with breed differences in behavior, which are found in genes that are highly expressed in the brain and enriched for neurobiological functions and developmental processes. Our results provide insight into the heritability and genetic architecture of complex behavioral traits, and suggest that dogs provide a powerful model for these questions.

Fecundity gene SNPS as informative markers for assessment of Indian goat genetic architecture

2015 ◽  
Author(s):  
A. Maitra ◽  
Rekha Sharma ◽  
Sonika Ahlawat ◽  
K. Borana ◽  
M. S. Tantia
Keyword(s):  
Genetic Distance ◽  
Genetic Architecture ◽  
Population Studies ◽  
Nucleotide Polymorphisms ◽  
Genetic Structuring ◽  
Single Nucleotide ◽  
Breeding Programs ◽  
Diversity Assessment ◽  
Pcr Rflp ◽  
Indian Goat

Single nucleotide polymorphisms (SNPs) are the most abundant form of DNA polymorphismwhich can be used as simple genetic markers for many breeding applications as well as for population studies. SNPs in fecundity (Fec) genes viz. BMPR1B, GDF9 and BMP15 were genotyped in Indian goat breeds to assess their basic population parameters and genetic structuring, using simple and economical methods of PCR-RFLP and Tetra-primer ARMS PCR. Three hundred and ninety one animals of seven different goat breeds differing in prolificacy, utility and geographic distribution were employed for diversity assessment at six loci in these Fec genes. Four loci were polymorphic in all the breeds with varied allelic frequencies. Statistical analysis revealed that breeds differed with respect to genetic variability as observed heterozygosity varied from 0.163 (Ganjam) to 0.359 (Jakhrana). Sangamneri and Osmanabadi were least differentiated (0.003) whereas Jakhrana and Black Bengal were most differentiated (0.048) on the basis of genetic distance. The genetic distance as well as PCA analysis indicated that breeds are grouped according to their geographical distribution. The genetic diversity based on fecundity genes presented here is an essential step towards the future exploitation of the available goat genetic resources in research and breeding programs.

scholarly journals Structural Covariance Network as an Endophenotype in Alzheimer’s Disease-Susceptible Single-Nucleotide Polymorphisms and the Correlations With Cognitive Outcomes

2021 ◽  
Vol 13 ◽  
Author(s):  
Hsin-I Chang ◽  
Yu-Tzu Chang ◽  
Chi-Wei Huang ◽  
Kuo-Lun Huang ◽  
Jung-Lung Hsu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gray Matter ◽  
Short Term Memory ◽  
Brain Network ◽  
Cognitive Outcomes ◽  
Nucleotide Polymorphisms ◽  
Genetic Loci ◽  
Single Nucleotide ◽  
Structural Covariance

The cognitive manifestations of Alzheimer’s disease (AD) are related to brain network degeneration, and genetic differences may mediate network degeneration. Several AD-susceptible loci have been reported to involve amyloid or tau cascades; however, their relationships with gray matter (GM) volume and cognitive outcomes have yet to be established. We hypothesized that single-nucleotide polymorphism genotype groups may interact with apolipoprotein E4 (ApoE4) status or independently exert an effect on cognitive outcomes. We also hypothesized that GM structural covariance networks (SCNs) may serve as an endophenotype of the genetic effect, which, in turn, may be related to neurobehavior test scores. Gray matter SCNs were constructed in 324 patients with AD using T1 magnetic resonance imaging with independent component analysis (ICA). We assessed the effects of 15 genetic loci (rs9349407, rs3865444, rs670139, rs744373, rs3851179, rs11136000, rs3764650, rs610932, rs6887649, rs7849530, rs4866650, rs3765728, rs34011, rs6656401, and rs597668) using additive, recessive, and dominant models on cognitive outcomes. Statistical analysis was performed to explore the independent role of each locus, interactions with ApoE4 status, and relationships to GM ICA network intensity score. For outcome measures, we used the Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI) total score, and short-term memory (STM) subscores, adjusted for the covariates of education, disease duration, and age. Clinically, the CD2AP G allele showed a protective role in MMSE, CASI total, and CASI-STM scores independently or via interactions with non-ApoE4 status, while the CR1 A genotype group was associated with lower STM subscores independent of ApoE4 status. Three loci showed synergic interactions with ApoE4: BIN 1, MS4A6A, and FTMT. Of the 15 meaningful ICA components, 5 SCNs (anterior and posterior hippocampus, right temporal, left thalamus, default mode network) showed relationships with general cognitive performance, in which only the ApoE4 and MS4A6A genotype groups were independently related to the hippocampus network. The genetic loci MS4A6A, BIN1, CLU, CR1, BIN1, PICALM, and FGF1 influenced the networks independently or in synergy. This study suggests that AD-susceptible loci may each exert clinical significance independently through interactions with ApoE4 status or through SCNs as an endophenotype and that this effect is associated with the cognitive outcomes.

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