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- Ahmad, Shafqat, et al.
(författare)
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Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan : the PROMIS study
- 2015
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Ingår i: BMC Medical Genetics. - : BioMed Central. - 1471-2350. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple genetic variants have been reliably associated with obesity-related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians.Methods: In 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score - GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age(2), sex, MI (yes/no), and population substructure.Results: Of 95 SNPs studied here, 73 showed directionally consistent effects on BMI as reported in Europeans. Each additional BMI-raising allele of the GRS was associated with 0.04 (SE = 0.01) kg/m(2) higher BMI (P = 4.5 x 10(-14)). We observed nominal evidence of interactions of CLIP1 rs11583200 (P-interaction = 0.014), CADM2 rs13078960 (P-interaction = 0.037) and GALNT10 rs7715256 (P-interaction = 0.048) with physical activity, and PTBP2 rs11165643 (P-interaction = 0.045), HIP1 rs1167827 (P-interaction = 0.015), C6orf106 rs205262 (P-interaction = 0.032) and GRID1 rs7899106 (P-interaction = 0.043) with smoking on BMI.Conclusions: Most BMI-associated loci have directionally consistent effects on BMI in Pakistanis and Europeans. There were suggestive interactions of established BMI-related SNPs with smoking or physical activity.
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- Haiman, Christopher A., et al.
(författare)
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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:12, s. 61-1210
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
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3. |
- Mavaddat, Nasim, et al.
(författare)
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Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:5, s. 036-036
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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4. |
- Sohel, Ahmed, et al.
(författare)
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Fitness trainers’ educational qualification and experience and its association with their trainees’ musculoskeletal pain: A cross-sectional study
- 2022
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Ingår i: Sports. - : MDPI. - 2075-4663. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- This is a cross-sectional study that examined the association between fitness trainers’ educational qualifications and experience, and the risk of their trainees’ musculoskeletal pain. The study included 1177 trainees (aged 15–60 years) from 74 fitness centers in Bangladesh. Data were collected by using the Nordic musculoskeletal questionnaire, including potential confounders such as demographic factors (e.g., age, occupation), and training-related factors (e.g., workout knowledge, overweight lifting). Multiple logistic regression was performed for a binary outcome (pain—yes or no), and a generalized linear model was fitted for the ordinal outcome (pain—sites of the body). The trainers’ lower experience (no or ≤1 year) was associated with higher odds of their trainees’ musculoskeletal pain (OR: 2.53, 95% CI: 1.18–5.44) compared to trainers with >5 years of experience; however, no association was found between the trainers’ education and the risk of their trainees’ musculoskeletal pain, after controlling for potential confounders. Similarly, the trainees trained by trainers with lower experience had more than two-time the risk of having pain in different sites (IRR: 2.04, 95% CI: 1.50–2.79). The trainers’ experience may play a pivotal role in the trainees’ musculoskeletal pain. Further study is warranted in this regard.
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5. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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