Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%(1,2). We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.

/pdf/common-polygenic-variation-contributes-to-risk-of-3uqwavl1v9.pdf

Common polygenic variation contributes to risk of schizophrenia and bipolar disorder

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

https://sites.oxy.edu/clint/physio/article/Geneticrelationshipbetweenfivepsychiatricdisorders.pdf

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.

https://science.sciencemag.org/content/sci/347/6217/78.full.pdf

Variation in cancer risk among tissues can be explained by the number of stem cell divisions

NAFLD is a clinical syndrome characterized by predominant macrovesicular steatosis of the liver. The clinical and histological phenotypes of NAFLD extend from a nonalcoholic fatty liver to NASH. Although the prevalence of NAFLD is increasing globally, and it is set to become the predominant cause of chronic liver disease in many parts of the world, the epidemiology and demographic characteristics of NAFLD vary worldwide. Indeed, the condition is associated with obesity and insulin resistance in most cases in the Western world, but the disease manifests at a lower BMI in Asian countries and many patients do not seem to have insulin resistance as determined using conventional methods. The similarities and differences in the epidemiology of NAFLD in different regions of the world are discussed and the potential role of genetics and insulin resistance in disease progression is also presented.

The global NAFLD epidemic

Background and aim: To update our 1996 review on the incidence of subarachnoid haemorrhage (SAH) and assess the relation of incidence with region, age, gender and time period Methods: We searched for studies on the incidence of SAH published until October 2005 The overall incidences with corresponding 95% confidence intervals were calculated We determined the relationship between the incidence of SAH and determinants by means of univariate Poisson regression Results: We included 51 studies (33 new), describing 58 study populations in 21 countries, observing 45 821 896 person-years Incidences per 100 000 person-years were 227 (95% CI 219 to 235) in Japan, 197 (181 to 213) in Finland, 42 (31 to 57) in South and Central America, and 91 (88 to 95) in the other regions With age category 45–55 years as the reference, incidence ratios increased from 010 (008 to 014) for age groups younger than 25 years to 161 (124 to 207) for age groups older than 85 years The incidence in women was 124 (109 to 142) times higher than in men; this gender difference started at age 55 years and increased thereafter Between 1950 and 2005, the incidence decreased by 06% (13% decrease to 01% increase) per year Conclusions: The overall incidence of SAH is approximately 9 per 100 000 person-years Rates are higher in Japan and Finland and increase with age The preponderance of women starts only in the sixth decade The decline in incidence of SAH over the past 45 years is relatively moderate compared with that for stroke in general

/pdf/incidence-of-subarachnoid-haemorrhage-a-systematic-review-12exoniivf.pdf

浩鮫島

Papers

Population-based study からみた神経予後不良因子の検討

妊娠・分娩時の脳出血 (特集産科緊急症--妊産婦死亡防止のために)

浩 鮫島

Papers

Population-based study からみた神経予後不良因子の検討

妊娠・分娩時の脳出血 (特集 産科緊急症--妊産婦死亡防止のために)

浩鮫島

妊娠・分娩時の脳出血 (特集産科緊急症--妊産婦死亡防止のために)