ABSTRACT
Detailed knowledge of how diversity in the sequence of the human genome affects phenotypic diversity depends on a comprehensive and reliable characterization of both sequences and phenotypic variation. Over the past decade, insights into this relationship have been obtained from whole-exome sequencing or whole-genome sequencing of large cohorts with rich phenotypic data1,2. Here we describe the analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank3. This constitutes a set of high-quality variants, including 585,040,410 single-nucleotide polymorphisms, representing 7.0% of all possible human single-nucleotide polymorphisms, and 58,707,036 indels. This large set of variants allows us to characterize selection based on sequence variation within a population through a depletion rank score of windows along the genome. Depletion rank analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation. We define three cohorts within the UK Biobank: a large British Irish cohort, a smaller African cohort and a South Asian cohort. A haplotype reference panel is provided that allows reliable imputation of most variants carried by three or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large-scale whole-genome sequencing studies. Using this formidable new resource, we provide several examples of trait associations for rare variants with large effects not found previously through studies based on whole-exome sequencing and/or imputation.
Subject(s)
Biological Specimen Banks , Databases, Genetic , Genetic Variation , Genome, Human , Genomics , Whole Genome Sequencing , Africa/ethnology , Asia/ethnology , Cohort Studies , Conserved Sequence , Exons/genetics , Genome, Human/genetics , Haplotypes/genetics , Humans , INDEL Mutation , Ireland/ethnology , Microsatellite Repeats , Polymorphism, Single Nucleotide/genetics , United KingdomABSTRACT
In studies of activity-based work environments, employees' prior attitude towards activity-based work environments has been identified as a potentially essential antecedent to how they perceive the new work environment. Using longitudinal data-collected once before and three times after moving to an activity-based office-we seek to reaffirm the moderating effect of this prior attitude on employee perceptions of privacy and psychological ownership in a sample from two smaller organisations (n = 38 combined). We also explore if employee attitude towards an activity-based work environment is related to personality dimensions. The findings support that prior employee attitude to an activity-based work environment moderates subsequent perceptions of privacy and psychological ownership. Only conscientiousness is significant when examining the association of personality and employee attitude towards an activity-based work environment. Implications of the findings and suggestions for future research are discussed.Practitioner summary: Questions remain about activity-based work environments. The data shows employee perceptions of privacy and psychological ownership are lower after moving to an activity-based office, but only for employees with less favourable attitudes towards activity-based environments beforehand. Conscientiousness is positively associated with employees' attitude towards activity-based environments before the move.
ABSTRACT
Meiotic recombinations contribute to genetic diversity by yielding new combinations of alleles. Recently, high-resolution recombination maps were inferred from high-density single-nucleotide polymorphism (SNP) data using linkage disequilibrium (LD) patterns that capture historical recombination events. The use of these maps has been demonstrated by the identification of recombination hotspots and associated motifs, and the discovery that the PRDM9 gene affects the proportion of recombinations occurring at hotspots. However, these maps provide no information about individual or sex differences. Moreover, locus-specific demographic factors like natural selection can bias LD-based estimates of recombination rate. Existing genetic maps based on family data avoid these shortcomings, but their resolution is limited by relatively few meioses and a low density of markers. Here we used genome-wide SNP data from 15,257 parent-offspring pairs to construct the first recombination maps based on directly observed recombinations with a resolution that is effective down to 10 kilobases (kb). Comparing male and female maps reveals that about 15% of hotspots in one sex are specific to that sex. Although male recombinations result in more shuffling of exons within genes, female recombinations generate more new combinations of nearby genes. We discover novel associations between recombination characteristics of individuals and variants in the PRDM9 gene and we identify new recombination hotspots. Comparisons of our maps with two LD-based maps inferred from data of HapMap populations of Utah residents with ancestry from northern and western Europe (CEU) and Yoruba in Ibadan, Nigeria (YRI) reveal population differences previously masked by noise and map differences at regions previously described as targets of natural selection.
Subject(s)
Chromosomes, Human/genetics , Recombination, Genetic/genetics , Sex Characteristics , Alleles , DNA-Binding Proteins/genetics , Europe/ethnology , Exons/genetics , Female , Genetics, Population , Haplotypes/genetics , Heterozygote , Histone-Lysine N-Methyltransferase/genetics , Humans , Linkage Disequilibrium/genetics , Male , Meiosis/genetics , Nigeria/ethnology , Pedigree , Polymorphism, Single Nucleotide/genetics , Sample Size , Selection, Genetic/genetics , UtahABSTRACT
We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1beta), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.
Subject(s)
Chromosomes, Human, Pair 17 , Diabetes Mellitus, Type 2/genetics , Hepatocyte Nuclear Factor 1-beta/genetics , Prostatic Neoplasms/genetics , Case-Control Studies , Genetic Predisposition to Disease , Haplotypes , Humans , Male , Polymorphism, Single NucleotideABSTRACT
Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.
Subject(s)
Fathers , Genetic Predisposition to Disease/genetics , Mothers , Polymorphism, Single Nucleotide/genetics , Alleles , Binding Sites , Breast Neoplasms/genetics , CCCTC-Binding Factor , Carcinoma, Basal Cell/genetics , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 7/genetics , DNA Methylation/genetics , Diabetes Mellitus, Type 2/genetics , Female , Genome, Human/genetics , Genomic Imprinting/genetics , Haplotypes , Humans , Iceland , Male , Pedigree , Repressor Proteins/metabolismABSTRACT
Organizations are facing a serious challenge with employee burnout, which leads to a loss of productivity and employee morale. Despite its importance, there is still a knowledge gap in understanding one of the key features of employee burnout, namely, the personal characteristics of employees. This research aims to determine if grit can alleviate employee burnout in organizations. The study conducted a survey of employees in service companies, and results showed that employee grit was negatively associated with burnout. Moreover, the study revealed that grit does not equally affect all three dimensions of burnout, with emotional exhaustion and depersonalization being the most affected by employee grit. Increasing employee grit is therefore a promising strategy for companies that want to mitigate the risk of employee burnout.
Subject(s)
Burnout, Professional , Humans , Burnout, Professional/prevention & control , Burnout, Professional/psychology , Emotions , Surveys and QuestionnairesABSTRACT
Using a longitudinal field survey, we collected data on how implementing an activity-based work environment impacts employees across time [1]. The sample consisted of 100 employees in a government organization implementing an activity-based working environment, with each employee surveyed on three time-points. The sample included all employees affected by the implementation. At each time-point, the response rate was 87%, 75%, and 69%, respectively. The sample was approximately 75% female at each time-point. Data collection took place about two months before the activity-based environment was implemented (condition 1), again about four months after implementation (condition 2), and finally, about nine months after implementation (condition 3). All data were collected using an online survey. The survey included questions on privacy, psychological ownership, and attitude towards activity-based work, in addition to questions on productivity, job satisfaction, job strain, and satisfaction with the work environment.
ABSTRACT
Social support from supervisors is a job resource that has been found to be an important antecedent to work engagement. However, there is a knowledge gap in understanding one of the key features of social support-i.e., supervisors' active-empathetic listening-and its relation to employees' work engagement. To bridge this gap, this study explores how supervisors' active-empathetic listening is associated with employees' work engagement. Using a national representative sample (N = 548), the results show that supervisors' active-empathetic listening has a significant positive relationship with employee work engagement. Additionally, we show that active-empathetic listening does not affect all three dimensions of work engagement equally, with dedication being the most affected by supervisors' active-empathetic listening. We argue that supportive leadership which uses conscious and active listening-centred communication is highly significant for employees' work engagement. Therefore, we suggest that organisations experiment in training their supervisors in active-empathetic listening as part of a broader strategy to increase employees' engagement at work.
Subject(s)
Empathy , Leadership , Nursing, Supervisory , Occupational Health , Work Engagement , Cross-Sectional Studies , Humans , Personal Satisfaction , Social SupportABSTRACT
OBJECTIVE: Rare copy number variants have been implicated in different neurodevelopmental disorders, with the same copy number variants often increasing risk of more than one of these phenotypes. In a discovery sample of 22 schizophrenia patients with an early onset of illness (10-15 years of age), the authors observed in one patient a maternally derived 15q11-q13 duplication overlapping the Prader-Willi/Angelman syndrome critical region. This prompted investigation of the role of 15q11-q13 duplications in psychotic illness. METHOD: The authors scanned 7,582 patients with schizophrenia or schizoaffective disorder and 41,370 comparison subjects without known psychiatric illness for copy number variants at 15q11-q13 and determined the parental origin of duplications using methylation-sensitive Southern hybridization analysis. RESULTS: Duplications were found in four case patients and five comparison subjects. All four case patients had maternally derived duplications (0.05%), while only three of the five comparison duplications were maternally derived (0.007%), resulting in a significant excess of maternally derived duplications in case patients (odds ratio=7.3). This excess is compatible with earlier observations that risk for psychosis in people with Prader-Willi syndrome caused by maternal uniparental disomy is much higher than in those caused by deletion of the paternal chromosome. CONCLUSIONS: These findings suggest that the presence of two maternal copies of a fragment of chromosome 15q11.2-q13.1 that overlaps with the Prader-Willi/Angelman syndrome critical region may be a rare risk factor for schizophrenia and other psychoses. Given that maternal duplications of this region are among the most consistent cytogenetic observations in autism, the findings provide further support for a shared genetic etiology between autism and psychosis.
Subject(s)
Chromosomes, Human, Pair 15/genetics , DNA Copy Number Variations/genetics , Schizophrenia/genetics , Adolescent , Adult , Age of Onset , Blotting, Southern , Child , Denmark , Female , Genetic Association Studies , Genotype , Humans , Male , Mothers , Prader-Willi Syndrome/genetics , Psychotic Disorders/genetics , Uniparental Disomy/genetics , United Kingdom , Young AdultABSTRACT
The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.
Subject(s)
Membrane Proteins/genetics , Neoplasm Proteins/genetics , Neoplasms/genetics , Polymorphism, Single Nucleotide , Telomerase/genetics , Aged , Carcinoma, Basal Cell/genetics , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Linkage Disequilibrium , Male , Middle Aged , Polymorphism, Single Nucleotide/physiology , Quantitative Trait Loci , Skin Neoplasms/geneticsABSTRACT
We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 x 10(-12)). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 x 10(-7)).
Subject(s)
Chromosomes, Human, Pair 8/genetics , Genetic Predisposition to Disease , Mutation/genetics , Urinary Bladder Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Base Sequence , Case-Control Studies , Chromosomes, Human, Pair 3/genetics , Female , Genetic Markers , Humans , Linkage Disequilibrium/genetics , Male , Middle AgedABSTRACT
We conducted a genome-wide SNP association study on prostate cancer on over 23,000 Icelanders, followed by a replication study including over 15,500 individuals from Europe and the United States. Two newly identified variants were shown to be associated with prostate cancer: rs5945572 on Xp11.22 and rs721048 on 2p15 (odds ratios (OR) = 1.23 and 1.15; P = 3.9 x 10(-13) and 7.7 x 10(-9), respectively). The 2p15 variant shows a significantly stronger association with more aggressive, rather than less aggressive, forms of the disease.