| 1. |
- 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.
|
|
| 2. |
- Zeggini, Eleftheria, et al.
(författare)
-
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
|
|
| 3. |
- Kathiresan, Sekar, et al.
(författare)
-
Common variants at 30 loci contribute to polygenic dyslipidemia
- 2009
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 56-65
-
Tidskriftsartikel (refereegranskat)abstract
- Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.
|
|
| 4. |
- Newton-Cheh, Christopher, et al.
(författare)
-
Genome-wide association study identifies eight loci associated with blood pressure
- 2009
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
-
Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
|
|
| 5. |
- Jacobsson, Bo, 1960, et al.
(författare)
-
Quantification of Ureaplasma urealyticum DNA in the amniotic fluid from patients in PTL and pPROM and its relation to inflammatory cytokine levels
- 2008
-
Ingår i: Acta Obstet Gynecol Scand. - 1600-0412. ; , s. 1-8
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To study the effect of the amniotic fluid quantity of Ureaplasma urealyticum DNA on inflammatory response levels in women with preterm labor (PTL) and preterm prelabor rupture of membranes (pPROM). Design. A prospective multi-center follow up study. Setting. Sahlgrenska University Hospital, Goteborg, Sweden and Turku University Hospital, Turku, Finland. Sample. Eleven U. urealyticum positive samples obtained after transabdominal amniocenteses in 197 women presenting with PTL and pPROM. Methods. The U. urealyticum positive samples were analyzed with real-time polymerase chain reaction, using the Lightcycler instrument with primers specific for U. urealyticum 16 S rDNA. The amniotic fluid samples were analyzed for tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta and IL-10 with enzyme-linked immunosorbent assays. Main outcome measures. Correlation between U. urealyticum DNA concentrations in the amniotic fluid and inflammatory cytokine levels. Results. The concentrations of U. urealyticum DNA varied between 0.024 and 934microg/mL. A significant correlation between U. urealyticum DNA and TNF-alpha level was observed. No correlation with the other cytokines was found. Women with PTLhad higher levels of U. urealyticum DNA and a different cytokine pattern than women with pPROM. Conclusions. U. urealyticum in the amniotic fluid induces an inflammatory reaction in a dose dependent manner and the quantity of U. urealyticum DNA is well correlated with the level of the inflammatory cytokine TNF-alpha.
|
|
| 6. |
- Jacobsson, Bo, 1960, et al.
(författare)
-
Quantification of Ureaplasma urealyticum DNA in the amniotic fluid from patients in PTL and pPROM and its relation to inflammatory cytokine levels
- 2009
-
Ingår i: Acta Obstet Gynecol Scand. ; 88:1, s. 63-70
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the effect of the amniotic fluid quantity of Ureaplasma urealyticum DNA on inflammatory response levels in women with preterm labor (PTL) and preterm prelabor rupture of membranes (pPROM). DESIGN: A prospective multi-center follow up study. SETTING: Sahlgrenska University Hospital, Goteborg, Sweden and Turku University Hospital, Turku, Finland. SAMPLE: Eleven U. urealyticum positive samples obtained after transabdominal amniocenteses in 197 women presenting with PTL and pPROM. METHODS: The U. urealyticum positive samples were analyzed with real-time polymerase chain reaction, using the Lightcycler instrument with primers specific for U. urealyticum 16 S rDNA. The amniotic fluid samples were analyzed for tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta and IL-10 with enzyme-linked immunosorbent assays. MAIN OUTCOME MEASURES: Correlation between U. urealyticum DNA concentrations in the amniotic fluid and inflammatory cytokine levels. RESULTS: The concentrations of U. urealyticum DNA varied between 0.024 and 934 microg/mL. A significant correlation between U. urealyticum DNA and TNF-alpha level was observed. No correlation with the other cytokines was found. Women with PTLhad higher levels of U. urealyticum DNA and a different cytokine pattern than women with pPROM. CONCLUSIONS: U. urealyticum in the amniotic fluid induces an inflammatory reaction in a dose dependent manner and the quantity of U. urealyticum DNA is well correlated with the level of the inflammatory cytokine TNF-alpha.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
