Anastasia Iliadou

Bio: Anastasia Iliadou is an academic researcher from Karolinska Institutet. The author has contributed to research in topics: Population & Birth weight. The author has an hindex of 33, co-authored 78 publications receiving 6539 citations.

Environmental and Heritable Factors in the Causation of Cancer — Analyses of Cohorts of Twins from Sweden, Denmark, and Finland

Abstract: Background The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases. Methods We combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer. Statistical modeling was used to estimate the relative importance of heritable and environmental factors in causing cancer at 11 of those sites. Results At least one cancer occurred in 10,803 persons among 9512 pairs of twins. An increased risk was found among the twins of affected persons for stomach, colorectal, lung, breast, and prostate cancer. Statistically significant effects of heritable factors were observed for prostate cancer (42 percent of the risk may be explained by heritable factors; 95 percent confidence interval, 29 to 50 percent), colorectal cancer (35 perce...

Risk of High Blood Pressure Among Young Men Increases With the Degree of Immaturity at Birth

Abstract: Background— Survivors of preterm birth constitute a new generation of young adults, but little is known about their long-term health. We investigated the association between gestational age (GA) and risk of high blood pressure (HBP) in young Swedish men and whether GA modified the risk of HBP; ie, whether HBP was related to being born small for gestational age (SGA). Methods and Results— This population-based cohort study included 329 495 Swedish men born in 1973 to 1981 who were conscripted for military service in 1993 to 2001. Multivariate linear- and logistic-regression analyses were performed. Main outcome measures were systolic and diastolic BPs at conscription. Linear-regression analyses showed that systolic BP increased with decreasing GA (regression coefficient −0.31 mm Hg/wk, P<0.001). Systolic and diastolic BPs both increased with decreasing birth weight for GA, but the association with systolic BP was most evident (regression coefficient −0.67 mm Hg per SD score in birth weight for GA, P<0.001)...

Autism and mental retardation among offspring born after in vitro fertilization

Abstract: Importance Between 1978 and 2010, approximately 5 million infants were born after in vitro fertilization (IVF) treatments Yet limited information on neurodevelopment after IVF exists, especially after the first year of life Objective To examine the association between use of any IVF and different IVF procedures and the risk of autistic disorder and mental retardation in the offspring Design, Setting, and Participants A population-based, prospective cohort study using Swedish national health registers Offspring born between 1982 and 2007 were followed up for a clinical diagnosis of autistic disorder or mental retardation until December 31, 2009 The exposure of interest was IVF, categorized according to whether intracytoplasmic sperm injection (ICSI) for male infertility was used and whether embryos were fresh or frozen For ICSI, whether sperm were ejaculated or surgically extracted was also considered Main Outcomes and Measures Relative risks (RRs) for autistic disorder and mental retardation and rates per 100 000 person-years, comparing spontaneously conceived offspring with those born after an IVF procedure and comparing 5 IVF procedures used in Sweden vs IVF without ICSI with fresh embryo transfer, the most common treatment We also analyzed the subgroup restricted to singletons Results Of the more than 25 million infants born, 30 959 (12%) were conceived by IVF and were followed up for a mean 10 (SD, 6) years Overall, 103 of 6959 children (15%) with autistic disorder and 180 of 15 830 (11%) with mental retardation were conceived by IVF The RR for autistic disorder after any procedure compared with spontaneous conception was 114 (95% CI, 094-139; 190 vs 156 per 100 000 person-years) The RR for mental retardation was 118 (95% CI, 101-136; 463 vs 398 per 100 000 person-years) For both outcomes, there was no statistically significant association when restricting analysis to singletons Compared with IVF without ICSI with fresh embryo transfer, there were statistically significantly increased risks of autistic disorder following ICSI using surgically extracted sperm and fresh embryos (RR, 460 [95% CI, 214-988]; 1357 vs 293 per 100 000 person-years); for mental retardation following ICSI using surgically extracted sperm and fresh embryos (RR, 235 [95% CI, 101-545]; 1441 vs 608 per 100 000 person-years); and following ICSI using ejaculated sperm and fresh embryos (RR, 147 [95% CI, 103-209]; 906 vs 608 per 100 000 person-years) When restricting the analysis to singletons, the risks of autistic disorder associated with ICSI using surgically extracted sperm were not statistically significant, but the risks associated with ICSI using frozen embryos were significant for mental retardation (with frozen embryos, RR, 236 [95% CI, 104-536], 1184 vs 506 per 100 000 person-years]; with fresh embryos, RR, 160 [95% CI, 100-257], 800 vs 506 per 100 000 person-years) Conclusions and Relevance Compared with spontaneous conception, IVF treatment overall was not associated with autistic disorder but was associated with a small but statistically significantly increased risk of mental retardation For specific procedures, IVF with ICSI for paternal infertility was associated with a small increase in the RR for autistic disorder and mental retardation compared with IVF without ICSI The prevalence of these disorders was low, and the increase in absolute risk associated with IVF was small

Two Common, Functional Polymorphisms in the Promoter Region of the β-Fibrinogen Gene Contribute to Regulation of Plasma Fibrinogen Concentration

Abstract: Plasma fibrinogen is a major risk factor for coronary heart disease, stroke, and peripheral artery disease. There is evidence that genetic variation in the beta-fibrinogen gene contributes to the rate of synthesis of fibrinogen, but the molecular mechanism underlying the genetic heritability of the plasma fibrinogen concentration is largely unknown. We evaluated the physiological roles of 5 common nucleotide substitutions in the promoter region of the beta-fibrinogen gene at positions -148, -249, -455, -854, and -993 from the transcriptional start site. Electrophoretic mobility shift assays revealed distinct differences in the binding characteristics of nuclear proteins between wild-type and mutant fragments of both the -455G/A and -854G/A polymorphisms, whereas no clear differences were observed for the -148C/T, -249C/T, and -993C/T sites. Transfection studies in HepG2 cells showed increased basal rates of transcription for both the G-to-A substitution at position -455 (+50%, P<0.05) and the G-to-A substitution at -854 (+51%, P<0.05). Additional transfection studies using proximal promoter constructs confirmed that both the -455A and -854A alleles independently enhance the basal rate of transcription of the beta-fibrinogen gene. The rare alleles of the nonrelated -455G/A and -854G/A polymorphisms were also associated with significantly increased plasma fibrinogen levels in healthy middle-aged men. Overall, the 2 polymorphisms together explained approximately 11% of the variation in plasma fibrinogen concentration. It is concluded that the -455G/A and -854G/A polymorphisms of the beta-fibrinogen gene are physiologically relevant mutations with a significant impact on the plasma fibrinogen concentration.

Cancer statistics, 2019.

Abstract: Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.

Human biochemical genetics

Abstract: So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Five years of GWAS discovery

Abstract: The past five years have seen many scientific and biological discoveries made through the experimental design of genome-wide association studies (GWASs). These studies were aimed at detecting variants at genomic loci that are associated with complex traits in the population and, in particular, at detecting associations between common single-nucleotide polymorphisms (SNPs) and common diseases such as heart disease, diabetes, auto-immune diseases, and psychiatric disorders. We start by giving a number of quotes from scientists and journalists about perceived problems with GWASs. We will then briefly give the history of GWASs and focus on the discoveries made through this experimental design, what those discoveries tell us and do not tell us about the genetics and biology of complex traits, and what immediate utility has come out of these studies. Rather than giving an exhaustive review of all reported findings for all diseases and other complex traits, we focus on the results for auto-immune diseases and metabolic diseases. We return to the perceived failure or disappointment about GWASs in the concluding section.