| 1. |
- Claussnitzer, Melina, et al.
(författare)
-
Leveraging cross-species transcription factor binding site patterns: from diabetes risk Loci to disease mechanisms.
- 2014
-
Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 156:1-2, s. 343-358
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative computational analysis of phylogenetic conservation with a complexity assessment of co-occurring transcription factor binding sites (TFBS) can identify cis-regulatory variants and elucidate their mechanistic role in disease. Analysis of established type 2 diabetes risk loci revealed a striking clustering of distinct homeobox TFBS. We identified the PRRX1 homeobox factor as a repressor of PPARG2 expression in adipose cells and demonstrate its adverse effect on lipid metabolism and systemic insulin sensitivity, dependent on the rs4684847 risk allele that triggers PRRX1 binding. Thus, cross-species conservation analysis at the level of co-occurring TFBS provides a valuable contribution to the translation of genetic association signals to disease-related molecular mechanisms.
|
|
| 2. |
- Kwan, Johnny S H, et al.
(författare)
-
Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels.
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6684-93
-
Tidskriftsartikel (refereegranskat)abstract
- Osteoprotegerin (OPG) is involved in bone homeostasis and tumor cell survival. Circulating OPG levels are also important biomarkers of various clinical traits, such as cancers and atherosclerosis. OPG levels were measured in serum or in plasma. In a meta-analysis of genome-wide association studies in up to 10,336 individuals from European and Asian origin, we discovered that variants >100 Kb upstream of the TNFRSF11B gene encoding OPG and another new locus on chromosome 17q11.2 were significantly associated with OPG variation. We also identified a suggestive locus on chromosome 14q21.2 associated with the trait. Moreover, we estimated that over half of the heritability of OPG levels could be explained by all variants examined in our study. Our findings provide further insight into the genetic regulation of circulating OPG levels.
|
|
| 3. |
- Lee, Tzong-Ru, et al.
(författare)
-
Key factors affecting customers’ willingness to use mobile coupons in a restaurant setting
- 2014
-
Ingår i: International Journal of Management and Enterprise Development. - : InderScience Publishers. - 1468-4330 .- 1741-8127. ; 13:3/4, s. 248-260
-
Tidskriftsartikel (refereegranskat)abstract
- For restaurants, the provision of coupons is a usual way of attracting people to the restaurant. Today, many restaurants consider how to use mobile advertising to promote their coupons (i.e., mobile coupons) in order to attract people and enhance its popularity. The purpose of this research is to identify what factors that affect customers' willingness to use mobile coupons in a restaurant setting. Five key factors that affect customers' willingness to use mobile coupons in a restaurant setting have been identified, from a base of 14 factors regarding customers' willingness to accept mobile advertising. The identified factors include price, customisation, promotion, entertainment, and sending time. This means that when customers use mobile coupons, the five identified factors will affect their willingness to use them. Restaurants can use the identified factors as a reference, when they try to develop new marketing strategies or want to enhance the effectiveness of mobile coupons.
|
|
| 4. |
- Lee, Tzong-Ru, et al.
(författare)
-
Managing the customer waiting problem in fast food restaurants in Taiwan through reengineering of the app ordering process
- 2014
-
Ingår i: Proceeding of the International Conference on Technology Innovation and Industrial Management. - Seoul, South Korea. ; , s. 40-48
-
Konferensbidrag (refereegranskat)abstract
- Purpose: The aim of this research is to manage the customer-waiting problem in Taiwanese fast food restaurants through reengineering of the APP ordering process.Design/methodology/approach: This research uses a literature review to identify differentapproaches of reengineering and use them to improve the APP ordering process used in Taiwanese fast food restaurants.Findings: This research has identified six approaches of reengineering, which can be applied to improve the APP ordering process in fast food restaurants. The application of thereengineering approaches, in the APP ordering process in Taiwanese fast food restaurants, generated four suggestions of how to improve the original APP ordering process.Research limitations/implications: The subsequent research can apply other research methods to improve the reliability and validity.Practical implications: The application of reengineering approaches to improve the APP ordering process in fast food restaurants can be used in other country’s food industry and be adapted to other industries as well. The research could also provide a basis for companies that want to implement the APP ordering system.Originality/value: This research clarifies the customer-waiting problem in the APP ordering process in Taiwanese fast food restaurants and applies reengineering approaches to improve the original APP ordering process.
|
|
| 5. |
- Moayyeri, Alireza, et al.
(författare)
-
Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
-
Tidskriftsartikel (refereegranskat)abstract
- Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
|
|
| 6. |
- Oei, Ling, et al.
(författare)
-
A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus
- 2014
-
Ingår i: Journal of Medical Genetics. - : BMJ Publishing Group. - 0022-2593 .- 1468-6244. ; 51:2, s. 122-131
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.AIM: To identify CNVs associated with osteoporotic bone fracture risk.METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies.RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk.CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
|
|
