| 31. |
- Chubb, Daniel, et al.
(författare)
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Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 366-1221
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Tidskriftsartikel (refereegranskat)abstract
- To identify variants for multiple myeloma risk, we conducted a genome-wide association study with validation in additional series totaling 4,692 individuals with multiple myeloma (cases) and 10,990 controls. We identified four risk loci at 3q26.2 (rs10936599, P = 8.70 x 10(-14)), 6p21.33 (rs2285803, PSORS1C2, P = 9.67 x 10(-11)), 17p11.2 (rs4273077, TNFRSF13B, P = 7.67 x 10(-9)) and 22q13.1 (rs877529, CBX7, P = 7.63 x 10(-16)). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy, as well as insight into the biological basis of predisposition.
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| 32. |
- Strikwerda-Brown, Cherie, et al.
(författare)
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Association of Elevated Amyloid and Tau Positron Emission Tomography Signal with Near-Term Development of Alzheimer Disease Symptoms in Older Adults Without Cognitive Impairment
- 2022
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 79:10, s. 975-985
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Tidskriftsartikel (refereegranskat)abstract
- Importance: National Institute on Aging-Alzheimer's Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD). Objective: To assess the clinical value of these biological criteria to identify older individuals without cognitive impairment who are at near-term risk of developing symptomatic AD. Design, Setting, and Participants: This longitudinal cohort study used data from 4 independent population-based cohorts (PREVENT-AD, HABS, AIBL, and Knight ADRC) collected between 2003 and 2021. Participants were older adults without cognitive impairment with 1 year or more of clinical observation after amyloid β and tau positron emission tomography (PET). Median clinical follow-up after PET ranged from 1.94 to 3.66 years. Exposures: Based on binary assessment of global amyloid burden (A) and a composite temporal region of tau PET uptake (T), participants were stratified into 4 groups (A+T+, A+T-, A-T+, A-T-). Presence (+) or absence (-) of neurodegeneration (N) was assessed using temporal cortical thickness. Main Outcomes and Measures: Each cohort was analyzed separately. Primary outcome was clinical progression to mild cognitive impairment (MCI), identified by a Clinical Dementia Rating score of 0.5 or greater in Knight ADRC and by consensus committee review in the other cohorts. Clinical raters were blind to imaging, genetic, and fluid biomarker data. A secondary outcome was cognitive decline, based on a slope greater than 1.5 SD below the mean of an independent subsample of individuals without cognitive impairment. Outcomes were compared across the biomarker groups. Results: Among 580 participants (PREVENT-AD, 128; HABS, 153; AIBL, 48; Knight ADRC, 251), mean (SD) age ranged from 67 (5) to 76 (6) years across cohorts, with between 55% (137/251) and 74% (95/128) female participants. Across cohorts, 33% to 83% of A+T+ participants progressed to MCI during follow-up (mean progression time, 2-2.72 years), compared with less than 20% of participants in other biomarker groups. Progression further increased to 43% to 100% when restricted to A+T+(N+) individuals. Cox proportional hazard ratios for progression to MCI in the A+T+ group vs other biomarker groups were all 5 or greater. Many A+T+ nonprogressors also showed longitudinal cognitive decline, while cognitive trajectories in other groups remained predominantly stable. Conclusions and Relevance: The clinical prognostic value of NIA-AA research criteria was confirmed in 4 independent cohorts, with most A+T+(N+) older individuals without cognitive impairment developing AD symptoms within 2 to 3 years..
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| 33. |
- Deming, Yuetiva, et al.
(författare)
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Sex-specific genetic predictors of Alzheimer’s disease biomarkers
- 2018
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 136:6, s. 857-872
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer’s disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF Aβ42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In Aβ42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p = 0.04) and rs13115400 near LINC00290 (p = 0.002). These loci showed stronger associations among females (β = − 0.03, p = 4.25 × 10−8; β = 0.03, p = 3.97 × 10−8) than males (β = − 0.02, p = 0.009; β = 0.01, p = 0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values < 0.02) but not males (p > 0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p = 0.004), driven by a stronger association among females (β = 0.05, p = 4.57 × 10−10) compared to males (β = 0.02, p = 0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (pfemale = 0.047; pmale = 0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p = 0.006; CLDN16 p = 0.002) but not males (p ≥ 0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD’s genetic architecture.
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| 34. |
- His, Mathilde, et al.
(författare)
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Lifestyle correlates of eight breast cancer-related metabolites : a cross-sectional study within the EPIC cohort
- 2021
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2).Methods: To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786).Results: For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34:2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed.Conclusions: These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cancer. Further research is needed to identify potential non-lifestyle correlates of the metabolites investigated.
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| 35. |
- Hohman, Timothy J, et al.
(författare)
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Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau.
- 2018
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 75:8
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Tidskriftsartikel (refereegranskat)abstract
- The strongest genetic risk factor for Alzheimer disease (AD), the apolipoprotein E (APOE) gene, has a stronger association among women compared with men. Yet limited work has evaluated the association between APOE alleles and markers of AD neuropathology in a sex-specific manner.To evaluate sex differences in the association between APOE and markers of AD neuropathology measured in cerebrospinal fluid (CSF) during life or in brain tissue at autopsy.This multicohort study selected data from 10 longitudinal cohort studies of normal aging and AD. Cohorts had variable recruitment criteria and follow-up intervals and included population-based and clinic-based samples. Inclusion in our analysis required APOE genotype data and either CSF data available for analysis. Analyses began on November 6, 2017, and were completed on December 20, 2017.Biomarker analyses included levels of β-amyloid 42, total tau, and phosphorylated tau measured in CSF. Autopsy analyses included Consortium to Establish a Registry for Alzheimer's Disease staging for neuritic plaques and Braak staging for neurofibrillary tangles.Of the 1798 patients in the CSF biomarker cohort, 862 were women, 226 had AD, 1690 were white, and the mean (SD) age was 70 [9] years. Of the 5109 patients in the autopsy cohort, 2813 were women, 4953 were white, and the mean (SD) age was 84 (9) years. After correcting for multiple comparisons using the Bonferroni procedure, we observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau (β=0.41; 95% CI, 0.27-0.55; P<.001) and phosphorylated tau (β=0.24; 95% CI, 0.09-0.38; P=.001), whereby APOE showed a stronger association among women compared with men. Post hoc analyses suggested this sex difference was present in amyloid-positive individuals (β=0.41; 95% CI, 0.20-0.62; P<.001) but not among amyloid-negative individuals (β=0.06; 95% CI, -0.18 to 0.31; P=.62). We did not observe sex differences in the association between APOE and β-amyloid 42, neuritic plaque burden, or neurofibrillary tangle burden.We provide robust evidence of a stronger association between APOE-ε4 and CSF tau levels among women compared with men across multiple independent data sets. Interestingly, APOE-ε4 is not differentially associated with autopsy measures of neurofibrillary tangles. Together, the sex difference in the association between APOE and CSF measures of tau and the lack of a sex difference in the association with neurofibrillary tangles at autopsy suggest that APOE may modulate risk for neurodegeneration in a sex-specific manner, particularly in the presence of amyloidosis.
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| 36. |
- Pick, Cari M., et al.
(författare)
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Fundamental social motives measured across forty-two cultures in two waves
- 2022
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- How does psychology vary across human societies? The fundamental social motives framework adopts an evolutionary approach to capture the broad range of human social goals within a taxonomy of ancestrally recurring threats and opportunities. These motives-self-protection, disease avoidance, affiliation, status, mate acquisition, mate retention, and kin care-are high in fitness relevance and everyday salience, yet understudied cross-culturally. Here, we gathered data on these motives in 42 countries (N = 15,915) in two cross-sectional waves, including 19 countries (N = 10,907) for which data were gathered in both waves. Wave 1 was collected from mid-2016 through late 2019 (32 countries, N = 8,998; 3,302 male, 5,585 female; M-age = 24.43, SD = 7.91). Wave 2 was collected from April through November 2020, during the COVID-19 pandemic (29 countries, N = 6,917; 2,249 male, 4,218 female; M-age = 28.59, SD = 11.31). These data can be used to assess differences and similarities in people's fundamental social motives both across and within cultures, at different time points, and in relation to other commonly studied cultural indicators and outcomes.
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| 37. |
- Schillemans, Tessa, et al.
(författare)
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Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis
- 2022
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Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD.Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed.Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged >= 65, 2) individuals with renal impairment, and 3) antiplatelet users.Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.
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| 38. |
- Chittani, Martina, et al.
(författare)
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TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives.
- 2015
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Ingår i: Journal of Hypertension. - 1473-5598. ; 33:6, s. 1301-1309
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Tidskriftsartikel (refereegranskat)abstract
- Thiazide diuretics have been recommended as a first-line antihypertensive treatment, although the choice of 'the right drug in the individual essential hypertensive patient' remains still empirical. Essential hypertension is a complex, polygenic disease derived from the interaction of patient's genetic background with the environment. Pharmacogenomics could be a useful tool to pinpoint gene variants involved in antihypertensive drug response, thus optimizing therapeutic advantages and minimizing side effects.
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| 39. |
- Deming, Timothy J., et al.
(författare)
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Polymers at the Interface with Biology
- 2018
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Ingår i: Biomacromolecules. - : AMER CHEMICAL SOC. - 1525-7797 .- 1526-4602. ; 19:8, s. 3151-3162
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 40. |
- Gentiluomo, Manuel, et al.
(författare)
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Mitochondrial DNA Copy-Number Variation and Pancreatic Cancer Risk in the Prospective EPIC Cohort
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:3, s. 681-686
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be sociated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma DAC) are very limited.Methods: To further our knowledge on this topic, we measured relative mtDNA copy number by a antitative real-time PCR assay in peripheral leukocyte samples of 476PDACcases and 357 controls sted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Results: We observed lower mtDNA copy number with advancing age (P = 6.54 x 10(-5)) and with a high dy mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol nsumption. We found an association between increased mtDNA copy number and decreased risk of veloping PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.160.79; P = 0.01] when mparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 5% CI, 0.07-0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an sociation between high mtDNA copy number and decreased risk in the stratum of normal weight, nsistent with the main analyses.Conclusions: Our results suggest a protective effect of a higher number of mitochondria, measured in ripheral blood leukocytes, on PDAC risk.Impact: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic ncer.
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