| 1. |
|
|
| 2. |
- 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.
|
|
| 3. |
|
|
| 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. |
- Ong, Ken K., et al.
(författare)
-
Genetic variation in LIN28B is associated with the timing of puberty
- 2009
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:6, s. 729-733
-
Tidskriftsartikel (refereegranskat)abstract
- The timing of puberty is highly variable(1). We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 x 10(-8)). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08-0.16; P = 2.8 x 10(-10); combined P = 3.6 x 10(-16)). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 x 10(-7); N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing(2), as the first genetic determinant regulating the timing of human pubertal growth and development.
|
|
| 6. |
- Romaguera, Dora, et al.
(författare)
-
Adherence to the Mediterranean Diet Is Associated with Lower Abdominal Adiposity in European Men and Women
- 2009
-
Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 139:9, s. 1728-1737
-
Tidskriftsartikel (refereegranskat)abstract
- Given the lack of consistent evidence of the relationship between Mediterranean dietary patterns and body fat, we assessed the cross-sectional association between adherence to a modified Mediterranean diet, BMI, and waist circumference (WC). A total of 497,308 individuals (70.7% women) aged 25-70 y from 10 European countries participated in this study. Diet was assessed at baseline using detailed validated country-specific questionnaires, and anthropometrical measurements were collected using standardized procedures. The association between the degree of adherence to the modified-Mediterranean Diet Score (mMDS) (including high consumption of vegetables, legumes, fruits and nuts, cereals, fish and seafood, and unsaturated: saturated fatty acids ratio; moderate alcohol intake; and low consumption of meat and meat products and dairy products) and BMI (kg.m(-2)) or WC (cm was modeled through mixed-effects linear regression, controlling for potential confounders. Overall, the mMDS was not significantly associated with BMI. Higher adherence to the Mediterranean diet was significantly associated with lower WC, for a given BMI, in both men (-0.09; 95% CI -0.14 to -0.04) and women (-0.06; 95% CI -0.10 to -0.01). The association was stronger in men (-0.20; 95% CI -0.23 to -0.17) and women (-0.17; 95% CI -0.21 to -0.13) from Northern European countries. Despite the observed heterogeneity among regions, results of this study suggest that adherence to a modified Mediterranean diet, high in foods of vegetable origin and unsaturated fatty acids, is associated with lower abdominal adiposity measured by WC in European men and women. J. Nutr. 139: 1728-1737, 2009.
|
|
| 7. |
- Travier, Noemie, et al.
(författare)
-
Smoking and body fatness measurements: A cross-sectional analysis in the EPIC-PANACEA study
- 2009
-
Ingår i: Preventive Medicine. - New York : Elsevier BV. - 1096-0260 .- 0091-7435. ; 49:5, s. 365-373
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. The present study investigates the cross-sectional relationship between tobacco smoking and body fatness. Methods. This cross-sectional study consisted of 469,543 men and women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1992 and 2000 providing anthropometric measurements and information on smoking. Adjusted multilevel mixed-effects linear regression models were used to assess the association between smoking and body fat mass. Results. The analyses showed that BMI and WC were positively associated with smoking intensity in current smokers but negatively associated with time since quitting in former smokers. When compared to never smokers, average current smokers (17 and 13 cig/day for men and women, respectively) showed a lower BMI. When average former smokers (men and women who had stopped smoking for 16 and 15 years, respectively) were compared to never smokers, higher BMI and WC were observed in men, whereas no significant associations were observed in women. Conclusions. This cross-sectional study suggests that smoking may be associated with body fatness and fat distribution. Although our findings cannot establish cause and effect, they suggest that providing information and support to those who want to stop may help in preventing weight gain and therefore weaken a barrier against stopping smoking. (C) 2009 Elsevier Inc. All rights reserved.
|
|
| 8. |
- Vimaleswaran, Karani Santhanakrishnan, et al.
(författare)
-
The Gly482Ser genotype at the PPARGC1A gene and elevated blood pressure : a meta-analysis involving 13,949 individuals
- 2008
-
Ingår i: Journal of applied physiology. - Bethesda : American physiological society. - 8750-7587 .- 1522-1601. ; 105:4, s. 1352-1358
-
Tidskriftsartikel (refereegranskat)abstract
- The protein encoded by the PPARGC1A gene is expressed at high levels in metabolically active tissues and is involved in the control of oxidative stress via reactive oxygen species detoxification. Several recent reports suggest that the PPARGC1A Gly482Ser (rs8192678) missense polymorphism may relate inversely with blood pressure. We used conventional meta-analysis methods to assess the association between Gly482Ser and systolic (SBP) or diastolic blood pressures (DBP) or hypertension in 13,949 individuals from 17 studies, of which 6,042 were previously unpublished observations. The studies comprised cohorts of white European, Asian, and American Indian adults, and adolescents from South America. Stratified analyses were conducted to control for population stratification. Pooled genotype frequencies were 0.47 (Gly482Gly), 0.42 (Gly482Ser), and 0.11 (Ser482Ser). We found no evidence of association between Gly482Ser and SBP [Gly482Gly: mean = 131.0 mmHg, 95% confidence interval (CI) = 130.5-131.5 mmHg; Gly482Ser mean = 133.1 mmHg, 95% CI = 132.6-133.6 mmHg; Ser482Ser: mean = 133.5 mmHg, 95% CI = 132.5-134.5 mmHg; P = 0.409] or DBP (Gly482Gly: mean = 80.3 mmHg, 95% CI = 80.0-80.6 mmHg; Gly482Ser mean = 81.5 mmHg, 95% CI = 81.2-81.8 mmHg; Ser482Ser: mean = 82.1 mmHg, 95% CI = 81.5-82.7 mmHg; P = 0.651). Contrary to previous reports, we did not observe significant effect modification by sex (SBP, P = 0.966; DBP, P = 0.715). We were also unable to confirm the previously reported association between the Ser482 allele and hypertension [odds ratio: 0.97, 95% CI = 0.87-1.08, P = 0.585]. These results were materially unchanged when analyses were focused on whites only. However, statistical evidence of gene-age interaction was apparent for DBP [Gly482Gly: 73.5 (72.8, 74.2), Gly482Ser: 77.0 (76.2, 77.8), Ser482Ser: 79.1 (77.4, 80.9), P = 4.20 x 10(-12)] and SBP [Gly482Gly: 121.4 (120.4, 122.5), Gly482Ser: 125.9 (124.6, 127.1), Ser482Ser: 129.2 (126.5, 131.9), P = 7.20 x 10(-12)] in individuals <50 yr (n = 2,511); these genetic effects were absent in those older than 50 yr (n = 5,088) (SBP, P = 0.41; DBP, P = 0.51). Our findings suggest that the PPARGC1A Ser482 allele may be associated with higher blood pressure, but this is only apparent in younger adults.
|
|
| 9. |
- 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.
|
|
