Copenhagen General Population Study
Copenhagen General Population Study
News Article | May 9, 2017
Having low body mass index (BMI) does not increase people's risk of developing Alzheimer's disease, scientists have said. Instead, people may go on to lose weight once they are diagnosed, as their behaviours, appetite and sense of smell are modified. The study, published in the Journal of Clinical Endocrinology & Metabolism, looks at blood and DNA samples from 95,578 participants in the Copenhagen General Population Study (CGPS) – 645 of whom developed Alzheimer's disease. Trending: Wild dolphins' immune systems are failing because of ocean pollution What is the Body Mass Index? The Body Mass Index (BMI) is used to quickly and simply assess a person's weight in regard to their height. It is calculated using the following formula: BMI (kg/m2) = mass (kg) / height (m)2 Previous research using data recorded from more than two million people in the UK had established that low BMI is associated with a heightened risk of Alzheimer's disease. Here, the researchers wanted to put these findings to a test. Most popular: Is your baby in pain? Brain scan can detect physical suffering in infants Instead of looking merely for associations, they went a step further and conducted what is known as "Mendelian randomisation analysis". This involved examining the participants' DNA for the presence of five genetic variants that are known to have a strong association with BMI. On top of the Copenhagen General Population Study, the scientists also used data from up to 249,796 individuals participating in the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Based on how many variants they had, all the participants were divided into four groups reflecting the likelihood of low BMI. The scientists then assessed the risk of developing Alzheimer's disease for each of these groups. "When we simply look at observational associations, we find the same as other previous studies. A low BMI is statistically linked to a higher risk of Alzheimer's. However, association does not mean causality", the study's senior author, Ruth Frikke-Schmidt, Chief Physician at Rigshospitalet in Copenhagen, told IBTimes UK. "Because genetic variants associated with low BMI are life-long and acquired totally randomly, it is a clean measurement of low BMI. It's good to use as a test of causality for body mass index". The researchers found that having genetic variants associated with low BMI did not increase the risk of Alzheimer's disease. Alzheimer's Society Research Communications Officer Dr Louise Walker commented:"Researching the links between BMI, weight and Alzheimer's disease is often complicated and findings are often contradictory. This research is a first step to untangle this complexity. "We need more large studies like this as they can tell us what patterns we need to investigate. The main limitation here however is that the scientists do not take into account in their analysis people who might have a low BMI for other reasons than genetic predispositions". The authors nevertheless came up with an explanation for the link observed between low BMI and the disease. They propose that patients' low BMI is due to behavioural changes, and appetite and weight loss they may suffer from in the early stages of the disease. Increasing people's BMI would probably have no impact on their risk of developing the disease. "The present research is important since it concludes that the association between low BMI and Alzheimer's disease is not of a causal nature. Changing public health recommendations based on observational data alone would cause more harm than benefits", Frikke-Schmidt concluded. You may be interested in:
News Article | May 9, 2017
WASHINGTON--A new large-scale genetic study found that low body mass index (BMI) is likely not a causal risk factor for Alzheimer's disease, as earlier research had suggested, according to a study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism. "Although prior studies found an association between Alzheimer's disease and low BMI, the new findings suggest this is not a causal relationship," said the study's senior author, Ruth Frikke-Schmidt, M.D., D.M.Sc., Ph.D., Chief Physician at Rigshospitalet in Copenhagen, Denmark, and Associate Research Professor at the University of Copenhagen. "The association can likely be explained by the fact that individuals with Alzheimer's disease are more likely to have low BMIs due to loss of appetite and weight loss in the early stages of the disease." More than 5 million Americans have Alzheimer's disease, according to the Alzheimer's Association's 2017 Alzheimer's Disease Facts and Figures Report. The disease affects the brain and is a common form of dementia. It is the sixth leading cause of death in the United States. To examine the association between Alzheimer's disease and low BMI, the researchers analyzed blood and DNA samples from 95,578 participants in the Copenhagen General Population Study (CGPS). Of the participants, 645 individuals developed Alzheimer's disease. The researchers analyzed the study participants' DNA for the presence of five genetic variants that have strong associations with BMI. Based on how many variants were found, participants were divided into four groups to reflect the likelihood of low BMI. The researchers also analyzed data from up to 249,796 individuals participating in the Genetic Investigation of ANthropometric Traits (GIANT) consortium for the genetic variants closely linked to low BMI. The analysis found the presence of the genetic variants tied to low BMI was not associated with increased risk of Alzheimer's disease. For comparison, the researchers examined if individuals with genetic variants connected to high BMI were more likely to have type 2 diabetes and did find the expected causal relationship. "We found individuals with lifelong low BMI due to genetic variation were not at increased risk of Alzheimer's disease," Frikke-Schmidt said. "Since genetic variants are not affected by other risk factors or diseases, this is a clean measure that can help to determine causality. The findings highlight that testing causality of a risk factor is pivotal before considering changing public health recommendations based on observational data alone." Other authors of the study include: Liv Tybjærg Nordestgaard and Anne Tybjærg-Hansen, of Rigshospitalet; and Børge G. Nordestgaard, of Herlev and Gentofte Hospital. All three also are affiliated with the University of Copenhagen. The research was supported by the Danish Medical Research Council, the Lundbeck Foundation, the Alzheimer Research Foundation, and the Research Fund at the Capital Region of Denmark. The study, "Body Mass Index and Risk of Alzheimer Disease: a Mendelian Randomization Study of 399,536 Individuals," will be published online at https:/ , ahead of print. Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world's oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions. The Society has more than 18,000 members, including scientists, physicians, educators, nurses and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at http://www. . Follow us on Twitter at @TheEndoSociety and @EndoMedia.
Zhang B.,Vanderbilt Epidemiology Center |
Shu X.-O.,Vanderbilt Epidemiology Center |
Delahanty R.J.,Vanderbilt Epidemiology Center |
Zeng C.,Vanderbilt Epidemiology Center |
And 194 more authors.
Journal of the National Cancer Institute | Year: 2015
Background: Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. Methods: We performed a meta-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5 216 302 women, including 113 178 events. In a consortium with individual-level data from 46 325 case patients and 42 482 control subjects, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16 003 case patients and 41 335 control subjects. Results: The pooled relative risk of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10 cm increase in height in the meta-analysis of prospective studies. In Mendelian randomization analysis, the odds ratio of breast cancer per 10 cm increase in genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The association was found in both premenopausal and postmenopausal women but restricted to hormone receptor-positive breast cancer. Analyses of height-associated variants identified eight new loci associated with breast cancer risk after adjusting for multiple comparisons, including three loci at 1q21.2, DNAJC27, and CCDC91 at genome-wide significance level P < 5 × 10-8. Conclusions: Our study provides strong evidence that adult height is a risk factor for breast cancer in women and certain genetic factors and biological pathways affecting adult height have an important role in the etiology of breast cancer. © The Author 2015. Published by Oxford University Press. All rights reserved.
Ali A.M.G.,University of Cambridge |
Ali A.M.G.,South Egypt Cancer Institute |
Schmidt M.K.,Netherlands Cancer Institute |
Bolla M.K.,University of Cambridge |
And 64 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2014
Background: Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts. Methods: A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for "moderate drinkers" versus nondrinkers. An analysis of individual participant data using Cox regression was carried out using data from 11 case cohorts. Results: We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate post-diagnosis alcohol consumption was not associated with overall survival [HR, 0.95; 95% confidence interval (CI), 0.85-1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80; 95% CI, 0.73-0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ERpositive disease, there was little evidence that pre- or postdiagnosis alcohol consumption is associated with breast cancer-specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer-specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease. Conclusion: There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer-specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer - specific mortality in ER-negative disease. Impact: Considering the totality of the evidence, moderate postdiagnosis alcohol consumption is unlikely to have a major adverse effect on the survival of women with breast cancer. ©2014 AACR.
PubMed | Center of Oncology of Poland, Karolinska Institutet, University of Newcastle, The Alfred Hospital and 76 more.
Type: Journal Article | Journal: Human molecular genetics | Year: 2014
Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16-1.33, P = 4.2 10(-10)) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04-1.11, P = 8.7 10(-6)) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07-1.23, P = 7.9 10(-5)) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer.