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Gender differences in first and secondhand smoke exposure, spirometric lung function and cardiometabolic health in the old order Amish: A novel population without female smoking

Due to their relatively homogeneous lifestyle and living environment, the Amish offer a novel opportunity to study the health associations of tobacco smoke exposure, particularly secondhand smoke. We hypothesized that secondhand smoke exposure is associated with worse pulmonary and cardiometabolic health. We examined cross-sectional data on 3568 Amish study participants...

Publisher Correction: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries

. Rich 9 24 Wendy Post 24 27 Braxton D. Mitchell 24 28 Adolfo Correa 24 James G. Wilson 0 24 Veikko Salomaa 1 24 Manolis Kellis 2 17 24 Mark J. Daly 17 21 23 24 Benjamin 24 M. Neale 24 McCarroll 17 21 22

Clinical impact of recent genetic discoveries in osteoporosis

Clinical impact of recent genetic discoveries in osteoporosis Braxton D Mitchell, Elizabeth A StreetenDepartment of Medicine and Program for Personalized and Genomic Medicine, University of Maryland

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries

Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both...

Genomic imprinting in diabetes

Genomic imprinting refers to a class of transmissible genetic effects in which the expression of the phenotype in the offspring depends on the parental origin of the transmitted allele. The DNA from one parent may be epigenetically modified so that only a single allele of the imprinted gene is expressed in the offspring. Although imprinting has an important role in the regulation...

Correlation of Circulating MMP-9 with White Blood Cell Count in Humans: Effect of Smoking

Background Matrix metalloproteinase-9 (MMP-9) is an emerging biomarker for several disease conditions, where white blood cell (WBC) count is also elevated. In this study, we examined the relationship between MMP-9 and WBC levels in apparently healthy smoking and non-smoking human subjects. Methods We conducted a cross-sectional study to assess the relationship of serum MMP-9 with...

Genetic Variation in the Platelet Endothelial Aggregation Receptor 1 Gene Results in Endothelial Dysfunction

Platelet Endothelial Aggregation Receptor 1 (PEAR1) is a newly identified membrane protein reported to be involved in multiple vascular and thrombotic processes. While most studies to date have focused on the effects of this receptor in platelets, PEAR1 is located in multiple tissues including the endothelium, where it is most highly expressed. Our first objective was to evaluate...

Polymorphisms in the SOCS7 gene and glucose homeostasis traits

Background SOCS7 is a member of the suppressor of cytokine signaling family of proteins and is expressed in skeletal muscle and islets. SOCS7 deficient mice develop islet hyperplasia in the setting of increased insulin sensitivity and normal glucose tolerance. The objective of this study was to determine if variants in SOCS7 play a role in variation of glucose and insulin levels...

Association between bilirubin and cardiovascular disease risk factors: using Mendelian randomization to assess causal inference

Background Elevated serum bilirubin has been associated with reduced risk of cardiovascular disease (CVD). However, serum bilirubin is also related with several potential confounders related to CVD, such as obesity. Mendelian randomization has been proposed as a method to address challenges to validity from confounding and reverse causality. It utilizes genotype to estimate...

Comparison of BMI and Physical Activity Between Old Order Amish Children and Non-Amish Children

OBJECTIVE The Old Order Amish (OOA) is a conservative Christian sect of European origin living in Pennsylvania. Diabetes is rare in adult OOA despite a mean BMI rivaling that in the general U.S. non-Hispanic white population. The current study examines childhood factors that may contribute to the low prevalence of diabetes in the OOA by comparing OOA children aged 8–19 years with...

Persistent Staphylococcus aureus Colonization Is Not a Strongly Heritable Trait in Amish Families

About 20% of adults are persistently colonized with S. aureus in the anterior nares. Host genetic factors could contribute susceptibility to this phenotype. The objective of this study was to determine whether the phenotype of persistent S. aureus colonization aggregates in family members who live in different households. Healthy adults and their eligible same sex siblings who...

Living the Good Life? Mortality and Hospital Utilization Patterns in the Old Order Amish

Lifespan increases observed in the United States and elsewhere throughout the developed world, have been attributed in part to improvements in medical care access and technology and to healthier lifestyles. To differentiate the relative contributions of these two factors, we have compared lifespan in the Old Order Amish (OOA), a population with historically low use of medical...

Time to Look Back and to Look Forward

K. Sreekumaran Nair 3 E. Dale Abel 1 Sharon G. Adler 0 Peter J. Dyck 7 Thomas W. Gardner 6 Kathryn M. Haskins 5 Gkhan Hotamisligil 4 Michael D. Jensen 3 Anna Krook Lawrence J. Mandarino 8 Braxton D ... . Mitchell 2 Jeffrey E. Pessin 11 James R. Sowers 12 Lori Sussel 9 Nick Wareham 10 Adrian Vella 3 0 Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Tor- of Medicine , Bronx, NY rance, CA 1

Modeled nitrate levels in well water supplies and prevalence of abnormal thyroid conditions among the Old Order Amish in Pennsylvania

Briseis Aschebrook-Kilfoy 0 Sonya L Heltshe John R Nuckols Mona M Sabra Alan R Shuldiner Braxton D Mitchell Matt Airola Theodore R Holford Yawei Zhang Mary H Ward 0 0 Occupational and Environmental

Polymorphisms in migraine-associated gene, atp1a2, and ischemic stroke risk in a biracial population: the genetics of early onset stroke study

In a recent meta-analysis migraine was associated with a two-fold increase in stroke risk. While the mechanism driving this association is unknown, one intriguing hypothesis is that migraineurs are genetically predisposed to developing ischemic stroke. Mutations in the ATP1A2 gene are implicated in familial hemiplegic migraine type II and increase the severity of ischemic brain...

Homozygosity by descent mapping of blood pressure in the Old Order Amish: evidence for sex specific genetic architecture

Background High blood pressure is a well established risk factor for morbidity and mortality acting through heart disease, stroke and cardiovascular disease. Genome wide scans have linked regions of nearly every human chromosome to blood pressure related traits. We have capitalized on beneficial qualities of the Old Order Amish of Lancaster, PA, a closed founder population with a...

PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological...

Rare Variants in Ischemic Stroke: An Exome Pilot Study

The genetic architecture of ischemic stroke is complex and is likely to include rare or low frequency variants with high penetrance and large effect sizes. Such variants are likely to provide important insights into disease pathogenesis compared to common variants with small effect sizes. Because a significant portion of human functional variation may derive from the protein...