| 1. |
- Estrada, Karol, et al.
(author)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Journal article (peer-reviewed)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 2. |
- Wang, Thomas J, et al.
(author)
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Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
- 2010
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In: Lancet. - 1474-547X. ; 376:9736, s. 180-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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| 3. |
- Butler, Geraldine, et al.
(author)
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Evolution of pathogenicity and sexual reproduction in eight Candida genomes.
- 2009
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 459:7247, s. 657-62
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Journal article (peer-reviewed)abstract
- Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
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| 4. |
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| 5. |
- Bose, Prosenjit, et al.
(author)
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Online routing in convex subdivisions
- 2000
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In: Algorithms and Computation. - Berlin : Encyclopedia of Global Archaeology/Springer Verlag. - 3540412557 ; , s. 47-59
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Conference paper (peer-reviewed)abstract
- We consider online routing algorithms for finding paths between the vertices of plane graphs. We show (1) there exists a routing algorithm for arbitrary triangulations that has no memory and uses no randomization, (2) no equivalent result is possible for convex subdivisions, (3) there is no competitive online routing algorithm under the Euclidean distance metric in arbitrary triangulations, and (4) there is no competitive online routing algorithm under the link distance metric even when the input graph is restricted to be a Delaunay, greedy, or minimum-weight triangulation.
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| 6. |
- Bose, Prosenjit, et al.
(author)
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Online routing in convex subdivisions
- 2002
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In: International journal of computational geometry and applications. - 0218-1959. ; 12:4, s. 283-295
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Journal article (peer-reviewed)abstract
- We consider online routing algorithms for finding paths between the vertices of plane graphs. We show (1) there exists a routing algorithm for arbitrary triangulations that has no memory and uses no randomization, (2) no equivalent result is possible for convex subdivisions, (3) there is no competitive online routing algorithm under the Euclidean distance metric in arbitrary triangulations, and (4) there is no competitive online routing algorithm under the link distance metric even when the input graph is restricted to be a Delaunay, greedy, or minimum-weight triangulation.
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| 7. |
- Brodnik, Andrej, et al.
(author)
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Membership in constant time and almost-minimum space
- 1999
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In: SIAM journal on computing (Print). - 0097-5397 .- 1095-7111. ; 28:5, s. 1627-1640
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Journal article (peer-reviewed)abstract
- This paper deals with the problem of storing a subset of elements from the bounded universe $\mathcal{M} = \{0, \ldots, M-1\}$ so that membership queries can be performed efficiently. In particular, we introduce a data structure to represent a subset of $N$ elements of $\mathcal{M}$ in a number of bits close to the information-theoretic minimum, $B = \left\lceil \lg {M\choose N} \right\rceil$, and use the structure to answer membership queries in constant time.
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| 8. |
- Brodnik, Andrej, et al.
(author)
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Neighbours on a grid
- 1996
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In: Algorithm Theory - SWAT'96. - Berlin : Encyclopedia of Global Archaeology/Springer Verlag. - 3540614222 ; , s. 309-320
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Conference paper (peer-reviewed)abstract
- We address the problem of a succinct static data structure representing points on an M × M grid (M = 2m where m is size of a word) that permits to answer the question of finding the closest point to a query point under the L ∞ or L 1 norm in constant time. Our data structure takes essentially minimum space. These results are extended to d dimensions under L ∞.
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| 9. |
- Brodnik, Andrej, et al.
(author)
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Resizable arrays in optimal time and space
- 1999
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In: Algorithms and Data Structures. - Berlin : Encyclopedia of Global Archaeology/Springer Verlag. - 3540662790 ; , s. 37-48
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Conference paper (peer-reviewed)abstract
- We present simple, practical and efficient data structures for the fundamental problem of maintaining a resizable one-dimensional array, A[l..l + n - 1], of fixed-size elements, as elements are added to or removed from one or both ends. Our structures also support access to the element in position i. All operations are performed in constant time. The extra space (i.e., the space used past storing the n current elements) is O(√n) at any point in time. This is shown to be within a constant factor of optimal, even if there are no constraints on the time. If desired, each memory block can be made to have size 2k - c for a specified constant c, and hence the scheme works effectively with the buddy system. The data structures can be used to solve a variety of problems with optimal bounds on time and extra storage. These include stacks, queues, randomized queues, priority queues, and deques.
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| 10. |
- Brodnik, Andrej, et al.
(author)
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Trans-dichotomous algorithms without multiplication : some upper and lower bounds
- 1997
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In: Algorithms and Data Structures. - Berlin : Encyclopedia of Global Archaeology/Springer Verlag. - 9783540633075 ; , s. 426-439
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Conference paper (peer-reviewed)abstract
- We show that on a RAM with addition, subtraction, bitwise Boolean operations and shifts, but no multiplication, there is a transdichotomous solution to the static dictionary problem using linear space and with query time log n(log log n)1+0(1). On the way, we show that two w-bit words can be multiplied in time (log w)1+0(1) and that time (log w) is necessary, and that (log log w) time is necessary and sufficient for identifying the least significant set bit of a word.
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