A survey of the genetics of stomach, liver, and adipose gene expression from a morbidly obese cohort

Abstract

S Y N OPSIS During a five year period at the Harlem Hospital Center nine heroin addicts were seen with strokes. Four occurred after loss of consciousness following intravenous heroin. Two occurred in patients using heroin at the time, but were not related to overdose or to a particular recent injection. The youth of these patients and lack of other predisposing factors suggests that heroin played a role in their strokes. In the other three patients, the relationships of stroke to heroin is less persuasive. There are several possible mechanisms by which heroin abuse could lead to stroke.A variety of medical (Louria et al., 1967) and neurological (Richter et al., 1973;Richter and Pearson, 1975) In 1970, a 25 year old heroin addict injected himself intravenously and within an hour noticed weakness which remained for a few days. He was unable to recall if the heroin he gave himself at that time was more than his usual amount, or if it had been his first injection after a period of abstinence.At the age of 26 years, he began sniffing cocaine and during this period of about two weeks did not take heroin. Then, feeling uncomfortably 'high' on cocaine, he gave himself his usual dose of heroin intravenously and became abruptly unresponsive. Brought to Harlem Hospital, he was comatose with a respiratory rate of 3/min and pinpoint pupils. There was prompt response to nallorphine 10 mg intravenously: respiration increased to 1 6/min, pupils became mid-position, and he awoke. He was lethargic and had mild difficulty in naming, moderate agraphia (writing with his left hand), alexia, right homonymous hemianopia, right facial weakness, flaccid paralysis of the right arm, and moderate weakness of the right leg. Position sense was decreased in the right fingers, and there were decreased deep tendon reflexes of the right limbs.White blood cell count was 13 250/ml (700O polymorphonuclears, 27% lymphocytes, 2% monocytes,

Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits

“…The larger number of adipose eQTLs observed in comparison to that in previous adipose eQTL studies might be due to the larger sample size, denser imputation, and/or analysis of a larger number of transcripts; some differences might be due to different microarray platforms, statistical methodology, and p value thresholds (Table S6). 10,11,37 30% of the cis-eQTLs discovered in METSIM at p < 5 3 10 À6 showed consistent allelic direction of effect in the MuTHER study, and 79.1% of the cis-eQTLs reported in MuTHER at this threshold showed a consistent direction of effect in METSIM (Table S7).…”

“…10,11,37 Using these eQTLs, we implicated 50 genes that were distinct from the initial locus annotations used as signposts for the GWAS loci (Table S8). For example, rs11231693 is associated with waist-hip ratio adjusted for BMI 16 and is located in the intron of MACROD1.…”

“…This locus has been reported in other tissues, including liver and omental fat, 77 but the target genes identified in our study do not overlap with the previous ones, suggesting a unique trans-regulatory network in subcutaneous adipose tissue. 11 Variants in this locus showed the strongest local association with the expression of SLC25A38, located~1 Mb away (p ¼ 1.7 3 10 À7 , Figure S7). Missense mutations in SLC25A38, which encodes a mitochondrial solute carrier, lead to congenital sideroblastic anemia characterized by defective erythropoiesis and mitochondrial iron overload.…”

“…9 Subcutaneous adipose eQTL studies have implicated genes involved in obesity and metabolic traits. [10][11][12][13] Recent GWASs for type 2 diabetes (T2D), cholesterol and triglyceride levels, body mass index, waist-hip ratio, and adiponectin have reported subcutaneous adipose eQTLs that are coincident with specific GWAS loci. [14][15][16][17] Similarly, a recent large GWAS for waist-hip ratio identified loci that were enriched for genes expressed in subcutaneous adipose tissue and for putative regulatory elements in adipocyte nuclei.…”

ATP2C2andDYX1C1are putative modulators of dyslexia‐related MMR

“…To identify eQTL effects, eQTL databases were analyzed (Borel et al., 2011; Dimas et al., 2009; Dixon et al., 2007; Fehrmann et al., 2011; Greenawalt et al., 2011; Grundberg et al., 2009; GTEx Consortium, 2015; Kim, Cho, Lee, & Webster, 2012; Kirsten et al., 2015; Mehta et al., 2013; Myers et al., 2007; Ramasamy et al., 2014; Schadt et al., 2008; Schröder et al., 2011; Veyrieras et al., 2008; Westra et al., 2013; Xia et al., 2012; Zeller et al., 2010). We only considered SNPs identified in brain or blood tissue and eQTLs had to be replicated in at least one study.…”