| 1. |
|
|
| 2. |
- Palumbo, A., et al.
(författare)
-
Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma
- 2008
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 22:2, s. 414-423
-
Tidskriftsartikel (refereegranskat)abstract
- The incidence of venous thromboembolism (VTE) is more than 1%omicron annually in the general population and increases further in cancer patients. The risk of VTE is higher in multiple myeloma (MM) patients who receive thalidomide or lenalidomide, especially in combination with dexamethasone or chemotherapy. Various VTE prophylaxis strategies, such as low-molecular-Weight heparin (LMWH), warfarin or aspirin, have been investigated in small, uncontrolled clinical studies. This manuscript summarizes the available evidence and recommends a prophylaxis strategy according to a risk-assessment model. Individual risk factors for thrombosis associated with thalidomide/lenalidomide-based therapy include age, history of VTE, central venous catheter, comorbidities (infections, diabetes, cardiac disease), immobilization, surgery and inherited thrombophilia. Myeloma-related risk factors include diagnosis and hyperviscosity. VTE is very high in patients who receive high-dose dexamethasone, doxorubicin or multiagent chemotherapy in combination with thalidomide or lenalidomide, but not with bortezomib. The panel recommends aspirin for patients with <= 1 risk factor for VTE. LMWH (equivalent to enoxaparin 40 mg per day) is recommended for those with two or more individual/myeloma-related risk factors. LMWH is also recommended for all patients receiving concurrent high-dose dexamethasone or doxorubicin. Full-dose warfarin targeting a therapeutic INR of 2-3 is an alternative to LMWH, although there are limited data in the literature with this strategy. In the absence of clear data from randomized studies as a foundation for recommendations, many of the following proposed strategies are the results of common sense or derive from the extrapolation of data from many studies not specifically designed to answer these questions. Further investigation is needed to define the best VTE prophylaxis.
|
|
| 3. |
- Wood, Laura D, et al.
(författare)
-
The genomic landscapes of human breast and colorectal cancers.
- 2007
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 318:5853, s. 1108-1113
-
Tidskriftsartikel (refereegranskat)abstract
- Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Harley, John B., et al.
(författare)
-
Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci
- 2008
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:2, s. 204-10
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.
|
|
| 8. |
- Lindgren, Cecilia M, et al.
(författare)
-
Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
- 2009
-
Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000508-
-
Tidskriftsartikel (refereegranskat)abstract
- To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
|
|
| 9. |
- Namjou, Bahram, et al.
(författare)
-
High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups
- 2009
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:4, s. 1085-1095
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder, with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in terms of the pathogenesis of SLE. STAT-1 and STAT-4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for involvement in SLE susceptibility. METHODS: Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large collection of 9,923 lupus patients and control subjects from different racial groups. DNA samples were obtained from the peripheral blood of patients with SLE and control subjects. Principal components analyses and population-based case-control association analyses were performed, and the P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated. RESULTS: We observed strong genetic associations with SLE and multiple SNPs located within STAT4 in different ethnic groups (Fisher's combined P = 7.02 x 10(-25)). In addition to strongly confirming the previously reported association in the third intronic region of this gene, we identified additional haplotypic association across STAT4 and, in particular, a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to its proximity to STAT4. CONCLUSION: Our findings indicate that STAT4 is likely to be a crucial component in SLE pathogenesis in multiple racial groups. Knowledge of the functional effects of this association, when they are revealed, might improve our understanding of the disease and provide new therapeutic targets.
|
|
| 10. |
- Prokopenko, Inga, et al.
(författare)
-
Variants in MTNR1B influence fasting glucose levels
- 2009
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 77-81
-
Tidskriftsartikel (refereegranskat)abstract
- To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
|
|
| 11. |
- Destree, Joshua D., et al.
(författare)
-
An ultraviolet search for interstellar CS
- 2009
-
Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 693:2009 March 1, s. 804-811
-
Tidskriftsartikel (refereegranskat)abstract
- High- and medium-resolution ultraviolet spectra from the Space Telescope Imaging Spectrograph (STIS) and the Goddard High Resolution Spectrograph (GHRS) were used to study the diatomic molecule CS through the C-X(0,0) band at 1401 Å. The band was modeled to verify profile shape. The rest wavelength of the C-X band is refined to a value of 1400.88 Å and a 3σ lower limit is set on the oscillator strength at 0.14 based on equivalent width upper limits of the A-X(0,0) CS Band at 2577 Å. The strength of the 1401 Å band is compared to other interstellar parameters and implications for CS formation and destruction are briefly discussed.
|
|
| 12. |
- Destree, Joshua D., et al.
(författare)
-
The Presence of Diffuse Interstellar Bands in the Spectra of Cool Stars
- 2007
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 664:2, s. 909-914
-
Tidskriftsartikel (refereegranskat)abstract
- Data from the Kitt Peak National Observatory (KPNO) coudé feed telescope were used to analyze the strength of three well-known diffuse interstellar bands (DIBs; 5780, 5797, and 6614 Å). Ten mid-A, mid-F, and mid-G stars with moderate reddening (EB-V=0.2-1.2) were observed, along with one reddened B0 dwarf for comparison. Synthetic spectra were calculated to remove the interference of stellar features. We report the detection of all three DIBs in A, F, and G stars. We also find the correlation of DIB strengths with E(B-V), in our sight lines, to be consistent with previous results from Herbig (1993), demonstrating that DIB strength is not dependent on the spectral type of the target star.
|
|
| 13. |
- Dispenzieri, A., et al.
(författare)
-
International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders
- 2009
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 23:2, s. 215-224
-
Forskningsöversikt (refereegranskat)abstract
- The serum immunoglobulin-free light chain (FLC) assay measures levels of free kappa and lambda immunoglobulin light chains. There are three major indications for the FLC assay in the evaluation and management of multiple myeloma and related plasma cell disorders (PCD). In the context of screening, the serum FLC assay in combination with serum protein electrophoresis (PEL) and immunofixation yields high sensitivity, and negates the need for 24-h urine studies for diagnoses other than light chain amyloidosis (AL). Second, the baseline FLC measurement is of major prognostic value in virtually every PCD. Third, the FLC assay allows for quantitative monitoring of patients with oligosecretory PCD, including AL, oligosecretory myeloma and nearly two-thirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial FLC measurements outperform PEL and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial FLC measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using FLC assay in place of 24-h urine PEL for monitoring or for serial measurements in PCD with measurable disease by serum or urine PEL. This paper provides consensus guidelines for the use of this important assay, in the diagnosis and management of clonal PCD.
|
|
| 14. |
- Forsgren, Anders, et al.
(författare)
-
Iterative solution of augmented systems arising in interior methods
- 2007
-
Ingår i: SIAM Journal on Optimization. - : Society for Industrial & Applied Mathematics (SIAM). - 1052-6234 .- 1095-7189. ; 18:2, s. 666-690
-
Tidskriftsartikel (refereegranskat)abstract
- Iterative methods are proposed for certain augmented systems of linear equations that arise in interior methods for general nonlinear optimization. Interior methods de. ne a sequence of KKT equations that represent the symmetrized ( but indefinite) equations associated with Newton's method for a point satisfying the perturbed optimality conditions. These equations involve both the primal and dual variables and become increasingly ill- conditioned as the optimization proceeds. In this context, an iterative linear solver must not only handle the ill- conditioning but also detect the occurrence of KKT matrices with the wrong matrix inertia. A one- parameter family of equivalent linear equations is formulated that includes the KKT system as a special case. The discussion focuses on a particular system from this family, known as the " doubly augmented system," that is positive definite with respect to both the primal and dual variables. This property means that a standard preconditioned conjugate- gradient method involving both primal and dual variables will either terminate successfully or detect if the KKT matrix has the wrong inertia. Constraint preconditioning is a well- known technique for preconditioning the conjugate- gradient method on augmented systems. A family of constraint preconditioners is proposed that provably eliminates the inherent ill- conditioning in the augmented system. A considerable benefit of combining constraint preconditioning with the doubly augmented system is that the preconditioner need not be applied exactly. Two particular " active- set" constraint preconditioners are formulated that involve only a subset of the rows of the augmented system and thereby may be applied with considerably less work. Finally, some numerical experiments illustrate the numerical performance of the proposed preconditioners and highlight some theoretical properties of the preconditioned matrices.
|
|
| 15. |
- Giralt, S., et al.
(författare)
-
International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100)
- 2009
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 23:10, s. 1904-1912
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma is the most common indication for high-dose chemotherapy with autologous stem cell support (ASCT) in North America today. Stem cell procurement for ASCT has most commonly been performed with stem cell mobilization using colony-stimulating factors with or without prior chemotherapy. The target CD34+ cell dose to be collected as well as the number of apheresis performed varies throughout the country, but a minimum of 2 million CD34+ cells/kg has been traditionally used for the support of one cycle of high-dose therapy. With the advent of plerixafor (AMD3100) (a novel stem cell mobilization agent), it is pertinent to review the current status of stem cell mobilization for myeloma as well as the role of autologous stem cell transplantation in this disease. On June 1, 2008, a panel of experts was convened by the International Myeloma Foundation to address issues regarding stem cell mobilization and autologous transplantation in myeloma in the context of new therapies. The panel was asked to discuss a variety of issues regarding stem cell collection and transplantation in myeloma especially with the arrival of plerixafor. Herein, is a summary of their deliberations and conclusions. Leukemia (2009) 23, 1904-1912; doi: 10.1038/leu.2009.127; published online 25 June 2009
|
|
| 16. |
- Hirsch, Joshua A., et al.
(författare)
-
Midterm clinical experience with a complex-shaped detachable platinum coil system for the treatment of cerebral aneurysms: Trufill DCS Orbit detachable coil system registry interim results
- 2007
-
Ingår i: Journal of Vascular and Interventional Radiology. - : Elsevier BV. - 1051-0443. ; 18:12, s. 1487-1494
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To report an interim analysis of the registry data and evaluate the performance of Trufill DCS Orbit coils in terms of the stability of initial aneurysmal occlusion. MATERIALS AND METHODS: From May 1, 2004, to February 1, 2006, 291 patients with ruptured or unruptured aneurysms were enrolled in a multiple-center global registry from 37 centers in the United States, Europe, and Latin America to be treated via endovascular embolization with Trufill DCS Orbit detachable platinum coils. Acute and long-term anatomic and clinical data were collected and evaluated. RESULTS: Initially, complete obliteration was reported in 187 of 300 treated aneurysms (62.3%) for which data were available; one treated aneurysm had no initial occlusion data. At follow-up (<= 1 year), 99 aneurysms were assessed. For 56 aneurysms with initial complete obliteration, 49 (87.5%) remained stable. The overall grade of occlusion of 99 aneurysms remained stable or improved in 81 cases (81.8%). Recanalization was seen in 16.2% of aneurysms (15 cases of coil compaction and one case of aneurysm growth); two aneurysms (2.0%) had coil migration. Five aneurysms (5.1%) underwent repeat treatment. CONCLUSIONS: The use of Trufill DCS Orbit coils for the endovascular occlusion of aneurysms allowed a favorable rate of initial complete obliteration, high packing density, and aneurysmal stability at follow-up as long as 1 year. Longer-term follow-up is needed to determine the long-term stability of aneurysmal occlusion.
|
|
| 17. |
- Milner, Joshua D, et al.
(författare)
-
Autoimmunity in severe combined immunodeficiency (SCID): lessons from patients and experimental models.
- 2008
-
Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 28 Suppl 1
-
Forskningsöversikt (refereegranskat)abstract
- Autoimmunity is observed in many immunodeficiencies and is thought to be mediated mainly by persistent infection. Severe combined immunodeficiency (SCID) is the most severe form of immunodeficiency and is also on occasion associated with autoimmune phenomena, usually in the form of the Omenn's Syndrome phenotype. Recent studies both in human and mice shed light into the pathogenesis of these two seemingly different conditions occurring together. Central tolerance, which is in charge of elimination of autoreactive T-cell clones, is defective in SCID because of markedly reduced expression of Aire, a transcriptional regulator for the expression of tissue-specific antigens in the thymus. Peripheral tolerance is also markedly decreased in SCID because of several factors including the expansion of T-cell clones as a consequence of the lymphopenia observed in these condition as well as a diminished number of T regulatory (FOXP3+)cells, allowing autoreactive T cells to proliferate and infiltrate various organs in the body of SCID. It is thus of no surprise when both central and peripheral tolerance are impaired that autoimmunity can be observed in SCID.
|
|
| 18. |
- Nene, Vishvanath, et al.
(författare)
-
Genome sequence of Aedes aegypti, a major arbovirus vector.
- 2007
-
Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5832, s. 1718-23
-
Tidskriftsartikel (refereegranskat)abstract
- We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
|
|
| 19. |
- Palumbo, A., et al.
(författare)
-
International Myeloma Working Group guidelines for the management of multiple myeloma patients ineligible for standard high-dose chemotherapy with autologous stem cell transplantation
- 2009
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 23:10, s. 1716-1730
-
Forskningsöversikt (refereegranskat)abstract
- In 2005, the first guidelines were published on the management of patients with multiple myeloma (MM). An expert panel reviewed the currently available literature as the basis for a set of revised and updated consensus guidelines for the diagnosis and management of patients with MM who are not eligible for autologous stem cell transplantation. Here we present recommendations on the diagnosis, treatment of newly diagnosed non-transplant-eligible patients and the management of complications occurring during induction therapy among these patients. These guidelines will aid the physician in daily clinical practice and will ensure optimal care for patients with MM. Leukemia (2009) 23, 1716-1730; doi: 10.1038/leu.2009.122; published online 4 June 2009
|
|
| 20. |
- Simon, Joshua D., et al.
(författare)
-
Variable Sodium Absorption in a Low-extinction Type Ia Supernova
- 2009
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 702, s. 1157-1170
-
Tidskriftsartikel (refereegranskat)abstract
- Recent observations have revealed that some Type Ia supernovae exhibit narrow, time-variable Na I D absorption features. The origin of the absorbing material is controversial, but it may suggest the presence of circumstellar gas in the progenitor system prior to the explosion, with significant implications for the nature of the supernova (SN) progenitors. We present the third detection of such variable absorption, based on six epochs of high-resolution spectroscopy of the Type Ia supernova SN 2007le from the Keck I Telescope and the Hobby-Eberly Telescope. The data span a time frame of approximately three months, from 5 days before maximum light to 90 days after maximum. We find that one component of the Na I D absorption lines strengthened significantly with time, indicating a total column density increase of ~2.5 × 1012 cm-2. The data limit the typical timescale for the variability to be more than 2 days but less than 10 days. The changes appear to be most prominent after maximum light rather than at earlier times when the ultraviolet flux from the SN peaks. As with SN 2006X, we detect no change in the Ca II H and K absorption lines over the same time period, rendering line-of-sight effects improbable and suggesting a circumstellar origin for the absorbing material. Unlike the previous two supernovae exhibiting variable absorption, SN 2007le is not highly reddened (E B - V = 0.27 mag), also pointing toward circumstellar rather than interstellar absorption. Photoionization calculations show that the data are consistent with a dense (107 cm-3) cloud or clouds of gas located ~0.1 pc (3 × 1017 cm) from the explosion. These results broadly support the single-degenerate scenario previously proposed to explain the variable absorption, with mass loss from a nondegenerate companion star responsible for providing the circumstellar gas. We also present possible evidence for narrow Hα emission associated with the SN, which will require deep imaging and spectroscopy at late times to confirm. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and NASA. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation. Based in part on observations obtained with the Hobby-Eberly Telescope, which is a joint project of the University of Texas at Austin, the Pennsylvania State University, Stanford University, Ludwig-Maximilians-Universität München, and Georg-August-Universität Göttingen.
|
|
| 21. |
- Willer, Cristen J., et al.
(författare)
-
Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
- 2009
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 25-34
-
Tidskriftsartikel (refereegranskat)abstract
- Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
|
|
| 22. |
- Wyner, Joshua D., et al.
(författare)
-
The genetics of motor disinhibition : a longitudinal analysis of the Go/NoGo task in twins
- 2009
-
Ingår i: Behavior Genetics. - : Springer Science and Business Media LLC. - 0001-8244 .- 1573-3297. ; 39:6, s. 692-692
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- To understand the etiology of antisocial behavior it is essential to investigate the origins of inhibition and impulsivity. While impulsive personality traits (such as those examined by the Barrett Impulsivity Scale) appear to increase over time, motor impulsivity (as measured by stop-signal tasks) appears to decrease. To investigate the origins of this change in motor impulsivity in more detail, we examined the genetic and environmental influences on performance in a visual Go/NoGo task for twins from the USC Twin Project. Errors of commission (NoGo errors) were used to measure motor impulsivity and were assessed longitudinally on up to three occasions at ages 9–10, ages 12–13, and ages 14–15 years old. In addition to classical biometric genetic models to investigate developmental changes in genetic (A), shared (C) and non-shared (E) environmental influences across age, we also employed latent growth curve modeling to investigate genetic and environmental influences on individual differences in change in impulsivity across age. Univariate model fitting results suggest a primarily A and E origin for NoGo task performance within each of the three occasions with estimates for the genetic contribution ranging from A=0.20–0.30. Over time, subjects task performance tended to improve (i.e., fewer errors of commission), phenotypically. Growth curve models suggest that this improvement over time is primarily due to unique environmental effects, which increased in importance with age. Genetic effects, in contrast, played a key roll in determining initial error levels. Taken together, these results suggest that the genetic influences on impulsive behavior take effect early in life, prior to the onset of adolescence, and that environmental influences play an increasingly important role during development. The significance of these findings is discussed, along with implications for further research
|
|
