Author
Debbie A Lawlor
Other affiliations: Southampton General Hospital, University of Vermont, Bradford Royal Infirmary ...read more
Bio: Debbie A Lawlor is an academic researcher from University of Bristol. The author has contributed to research in topics: Population & Body mass index. The author has an hindex of 147, co-authored 1114 publications receiving 101123 citations. Previous affiliations of Debbie A Lawlor include Southampton General Hospital & University of Vermont.
Papers published on a yearly basis
Papers
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TL;DR: In this paper, the authors performed a simulation study comprising different scenarios that could motivate covariable adjustment in a GWAS and analyzed real data to assess the influence of using covariable-adjusted summary association results in two-sample MR.
Abstract: Background Two-sample Mendelian randomization (MR) allows the use of freely accessible summary association results from genome-wide association studies (GWAS) to estimate causal effects of modifiable exposures on outcomes. Some GWAS adjust for heritable covariables in an attempt to estimate direct effects of genetic variants on the trait of interest. One, both or neither of the exposure GWAS and outcome GWAS may have been adjusted for covariables. Methods We performed a simulation study comprising different scenarios that could motivate covariable adjustment in a GWAS and analysed real data to assess the influence of using covariable-adjusted summary association results in two-sample MR. Results In the absence of residual confounding between exposure and covariable, between exposure and outcome, and between covariable and outcome, using covariable-adjusted summary associations for two-sample MR eliminated bias due to horizontal pleiotropy. However, covariable adjustment led to bias in the presence of residual confounding (especially between the covariable and the outcome), even in the absence of horizontal pleiotropy (when the genetic variants would be valid instruments without covariable adjustment). In an analysis using real data from the Genetic Investigation of ANthropometric Traits (GIANT) consortium and UK Biobank, the causal effect estimate of waist circumference on blood pressure changed direction upon adjustment of waist circumference for body mass index. Conclusions Our findings indicate that using covariable-adjusted summary associations in MR should generally be avoided. When that is not possible, careful consideration of the causal relationships underlying the data (including potentially unmeasured confounders) is required to direct sensitivity analyses and interpret results with appropriate caution. Key messages Summary genetic associations from large genome-wide associations studies (GWAS) have been increasingly used in two-sample Mendelian randomization (MR) analyses. Many GWAS adjust for heritable covariates in an attempt to estimate direct genetic effects on the trait of interest. In an extensive simulation study, we demonstrate that using covariable-adjusted summary associations may bias MR analyses. The bias largely depends on the underlying causal structure, specially the presence of unmeasured common causes between the covariable and the outcome. Our findings indicate that using covariable-adjusted summary associations in MR should generally be avoided.
15 citations
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TL;DR: GFR measurement appears to play a useful role in the subset of older women without pre-existing CVD who are at higher risk of premature CVD death, and the effect on CVD mortality is partly explained by existing CVD and its risk factors.
Abstract: Background. The prognostic value of reduced glomerular filtration rate (GFR) was examined in a community-based cohort of British women. Methods. Serum creatinine measurements were available for 90% (n = 3851) of a representative random sample of 4286 women aged 60-79 years. GFR was estimated using the Modification of Diet in Renal Disease equation. Hazard ratios (HR) were calculated using Cox regression with outcomes of all-cause and cardiovascular disease (CVD) mortality. Results. Eight hundred and thirty-two women (21.6%) had a GFR <60 ml/min/1.73 m(2). Over a median follow-up of 5.6 years, there were 318 deaths (100 CVD deaths). Women with GFR <60 ml/min/1.73 m(2) compared to all others showed only a borderline increased risk of all-cause mortality [HR 1.35 (95% confidence intervals: 0.99, 1.85)] and CVD mortality [1.34 (0.97, 1.85)]. Adjustment for conventional CVD risk factors had little impact. The association with CVD mortality was attenuated in women with pre-existing CVD [adjusted HR: 0.51 (0.24, 1.04)]. Only the subset of women without CVD at baseline were at risk for later CVD death [adjusted HR: 1.80 (1.13, 2.88)]. Conclusions. A substantial proportion of older British women have GFR <60 ml/min/1.73 m(2) without strong evidence for statistical association with all-cause mortality. The effect on CVD mortality is partly explained by existing CVD and its risk factors. GFR measurement appears only to play a useful role in the subset of older women without pre-existing CVD who are at higher risk of premature CVD death.
15 citations
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TL;DR: Limited epidemiological evidence suggests that low maternal iron status and anaemia in pregnancy may increase the risk of childhood respiratory and allergic outcomes.
Abstract: Background Limited epidemiological evidence suggests that low maternal iron status and anaemia in pregnancy may increase the risk of childhood respiratory and allergic outcomes.
Objectives To investigate the relation between maternal haemoglobin concentrations in pregnancy and childhood respiratory and allergic outcomes.
Methods In the Avon Longitudinal Study of Parents and Children (ALSPAC) we examined associations of maternal haemoglobin concentrations (g/dL) in pregnancy with hayfever, eczema, wheezing, doctor-diagnosed asthma, allergic sensitisation and total IgE at 7 years, and with lung function at 8-9 years in the offspring, after controlling for potential confounders (N=3234-5335).
Results Maternal haemoglobin was not associated with offspring hayfever, eczema, wheezing or asthma. However, the first haemoglobin measurement in pregnancy ( 28 weeks’ gestation) were negatively associated with allergic sensitisation (adjusted odds ratio (95% CI) per g/dl 0.91 (0.83 to 0.99) and 0.90 (0.83 to 0.98), respectively). The last haemoglobin measurement was also negatively associated with total IgE (adjusted geometric mean ratio 0.94 (0.88 to 0.99)). Anaemia (haemoglobin <11g/dL) in late pregnancy was negatively associated with Forced Vital Capacity (difference in standard deviation score -0.07 (-0.13 to -0.01)).
Conclusions and clinical relevance Lower maternal haemoglobin in pregnancy may be a risk factor for allergic sensitisation, elevated IgE and lower FVC in childhood, which may reflect effects of lower prenatal iron status. However, maternal haemoglobin was not associated with risk of childhood asthma or other allergic disorders.
This article is protected by copyright. All rights reserved.
15 citations
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TL;DR: The findings do not support an association between birth order and BMI or blood pressure, and associations tended to be in the opposite direction in males, although no statistical evidence for gender interactions was found.
Abstract: The association of birth order with later body mass index and blood pressure: a comparison between prospective cohort studies from the United Kingdom and Brazil
15 citations
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TL;DR: This study does not provide compelling evidence for associations between most early-life factors and body composition in adolescence, however, possible associations with dietary patterns and physical inactivity in early childhood require further investigation in other cohorts that have direct measurements of adolescent body composition.
Abstract: Previous studies have demonstrated associations between some early-life exposures and later obesity, but most have used body mass index in childhood or adulthood as the outcome. The objective of this study was to investigate whether early-life exposures were associated with directly measured fat and lean mass in adolescence. This study used data on 4750 mother–offspring pairs, collected as a part of the Avon Longitudinal Study of Parents and Children, Bristol, UK between 1991 and 1992; associations between behavioural exposures occurring from conception up to 5 years of age (maternal and paternal smoking during pregnancy, breastfeeding, age at introduction to solids, dietary patterns and physical inactivity during early childhood) and offspring body composition measured by dual-energy X-ray absorptiometry at ~15 years were assessed. After full adjustment for potential confounders, maternal smoking during pregnancy, having a junk food diet and spending more time watching television in early childhood were all associated with higher fat mass at age 15, whereas maternal smoking, having a healthy diet and playing computer games more frequently in early childhood were all associated with a higher lean mass at age 15. Associations with paternal smoking were generally weaker for both fat and lean mass, but as there was no strong statistical evidence for maternal vs paternal differences, confounding by social factors rather than a direct effect of maternal smoking cannot be ruled out. Early feeding was not associated with fat or lean mass at age 15. This study does not provide compelling evidence for associations between most early-life factors and body composition in adolescence. However, possible associations with dietary patterns and physical inactivity in early childhood require further investigation in other cohorts that have direct measurements of adolescent body composition.
15 citations
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28,685 citations
28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
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University of Manchester1, University of Barcelona2, St George's Hospital3, University of Marburg4, University of Texas Health Science Center at San Antonio5, Imperial College London6, University of Modena and Reggio Emilia7, University of Michigan8, Hokkaido University9, University of British Columbia10
TL;DR: It is recommended that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation.
Abstract: Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.
17,023 citations
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TL;DR: In this article, a randomized controlled trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly people was presented. But the authors did not discuss the effect of the combination therapy in patients living with systolic hypertension.
Abstract: ABCD
: Appropriate Blood pressure Control in Diabetes
ABI
: ankle–brachial index
ABPM
: ambulatory blood pressure monitoring
ACCESS
: Acute Candesartan Cilexetil Therapy in Stroke Survival
ACCOMPLISH
: Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension
ACCORD
: Action to Control Cardiovascular Risk in Diabetes
ACE
: angiotensin-converting enzyme
ACTIVE I
: Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events
ADVANCE
: Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation
AHEAD
: Action for HEAlth in Diabetes
ALLHAT
: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack
ALTITUDE
: ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints
ANTIPAF
: ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation
APOLLO
: A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People
ARB
: angiotensin receptor blocker
ARIC
: Atherosclerosis Risk In Communities
ARR
: aldosterone renin ratio
ASCOT
: Anglo-Scandinavian Cardiac Outcomes Trial
ASCOT-LLA
: Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm
ASTRAL
: Angioplasty and STenting for Renal Artery Lesions
A-V
: atrioventricular
BB
: beta-blocker
BMI
: body mass index
BP
: blood pressure
BSA
: body surface area
CA
: calcium antagonist
CABG
: coronary artery bypass graft
CAPPP
: CAPtopril Prevention Project
CAPRAF
: CAndesartan in the Prevention of Relapsing Atrial Fibrillation
CHD
: coronary heart disease
CHHIPS
: Controlling Hypertension and Hypertension Immediately Post-Stroke
CKD
: chronic kidney disease
CKD-EPI
: Chronic Kidney Disease—EPIdemiology collaboration
CONVINCE
: Controlled ONset Verapamil INvestigation of CV Endpoints
CT
: computed tomography
CV
: cardiovascular
CVD
: cardiovascular disease
D
: diuretic
DASH
: Dietary Approaches to Stop Hypertension
DBP
: diastolic blood pressure
DCCT
: Diabetes Control and Complications Study
DIRECT
: DIabetic REtinopathy Candesartan Trials
DM
: diabetes mellitus
DPP-4
: dipeptidyl peptidase 4
EAS
: European Atherosclerosis Society
EASD
: European Association for the Study of Diabetes
ECG
: electrocardiogram
EF
: ejection fraction
eGFR
: estimated glomerular filtration rate
ELSA
: European Lacidipine Study on Atherosclerosis
ESC
: European Society of Cardiology
ESH
: European Society of Hypertension
ESRD
: end-stage renal disease
EXPLOR
: Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination
FDA
: U.S. Food and Drug Administration
FEVER
: Felodipine EVent Reduction study
GISSI-AF
: Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation
HbA1c
: glycated haemoglobin
HBPM
: home blood pressure monitoring
HOPE
: Heart Outcomes Prevention Evaluation
HOT
: Hypertension Optimal Treatment
HRT
: hormone replacement therapy
HT
: hypertension
HYVET
: HYpertension in the Very Elderly Trial
IMT
: intima-media thickness
I-PRESERVE
: Irbesartan in Heart Failure with Preserved Systolic Function
INTERHEART
: Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries
INVEST
: INternational VErapamil SR/T Trandolapril
ISH
: Isolated systolic hypertension
JNC
: Joint National Committee
JUPITER
: Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin
LAVi
: left atrial volume index
LIFE
: Losartan Intervention For Endpoint Reduction in Hypertensives
LV
: left ventricle/left ventricular
LVH
: left ventricular hypertrophy
LVM
: left ventricular mass
MDRD
: Modification of Diet in Renal Disease
MRFIT
: Multiple Risk Factor Intervention Trial
MRI
: magnetic resonance imaging
NORDIL
: The Nordic Diltiazem Intervention study
OC
: oral contraceptive
OD
: organ damage
ONTARGET
: ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial
PAD
: peripheral artery disease
PATHS
: Prevention And Treatment of Hypertension Study
PCI
: percutaneous coronary intervention
PPAR
: peroxisome proliferator-activated receptor
PREVEND
: Prevention of REnal and Vascular ENdstage Disease
PROFESS
: Prevention Regimen for Effectively Avoiding Secondary Strokes
PROGRESS
: Perindopril Protection Against Recurrent Stroke Study
PWV
: pulse wave velocity
QALY
: Quality adjusted life years
RAA
: renin-angiotensin-aldosterone
RAS
: renin-angiotensin system
RCT
: randomized controlled trials
RF
: risk factor
ROADMAP
: Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention
SBP
: systolic blood pressure
SCAST
: Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke
SCOPE
: Study on COgnition and Prognosis in the Elderly
SCORE
: Systematic COronary Risk Evaluation
SHEP
: Systolic Hypertension in the Elderly Program
STOP
: Swedish Trials in Old Patients with Hypertension
STOP-2
: The second Swedish Trial in Old Patients with Hypertension
SYSTCHINA
: SYSTolic Hypertension in the Elderly: Chinese trial
SYSTEUR
: SYSTolic Hypertension in Europe
TIA
: transient ischaemic attack
TOHP
: Trials Of Hypertension Prevention
TRANSCEND
: Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease
UKPDS
: United Kingdom Prospective Diabetes Study
VADT
: Veterans' Affairs Diabetes Trial
VALUE
: Valsartan Antihypertensive Long-term Use Evaluation
WHO
: World Health Organization
### 1.1 Principles
The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …
14,173 citations
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TL;DR: It is suggested that the natural selection against large insertion/deletion is so weak that a large amount of variation is maintained in a population.
11,521 citations