SIMSAM – MEB node Transmitted and Acquired Determinants

of Health across Life-Span

Weimin YE

Professor in Medical Epidemiology

Department of Medical Epidemiology

and Biostatistics

Karolinska Institutet 2013-11-04

ki.se/meb

Transmitted and Acquired Determinants of Health across the

Life-Span

Coordinator:

Weimin Ye, Professor in Medical Epidemiology

Co-applicants:

Catarina Almqvist Malmros, Assistant Professor in Pediatric Epidemiology

Kamila Czene, Associate Professor in Cancer Epidemiology

Anastasia Iliadou, Assistant Professor in Epidemiology

Erik Ingelsson, Associate Professor in Epidemiology

Marie Reilly, Professor in Biostatistics

Other personnel

Henrik Larsson (wp2)

Ruslan Fomkin (wp7)

Pär Sparén (SocMob database)

Administration: Anna Berglund/Gabriella Malmsten

Organization

Regular meetings

Seminars

Biostatistical support

1. General support (Cecilia Lundholm)

2. Methodogical development

IT support, data management

Overall aims

Our general aim is to study transmitted and acquired determinants of important health conditions across the life-span, by improving and expanding the use of existing and emerging Swedish registers.

To address specific research questions on transmitted and acquired risk factors for somatic and psychiatric diseases across the life-span

To develop statistical methodology and computational strategies for valid analysis and efficient sharing and storage of data from population registers

WP 1 – Early life exposure to antibiotics, family history and

subsequent childhood health

WP 2 – The effect of psychiatric disorders in parents on adolescent

criminality in offspring

WP 3 – Prenatal exposures and familial contribution to obesity in

young adulthood, and its influence on subsequent cardiovascular

morbidity

WP 4 – Family history, transgenerational socioeconomic status and

cardiovascular diseases

WP 5 – Familial cancer: data for clinical counseling and cancer

genetics

WP 6 – Development of statistical methods for register-based

studies

WP 7 – To tackle performance, legal, and ethical challenges on accessing data stored in different authorities by developing cross-organizational database approach (Federated database approach)

New initiatives and collaborations

• Neurological disorders (Fang Fang, Karin Wirdefeldt):

ALS, Parkinson’s Disease, Myasthenia Gravis, etc,

Student scholarship from KI-NIH program), in

collaboration with Dept of Neurology, and NIEHS

• Stress and health (Katja Fall, Unnur Valdimarsdóttir,

Fang Fang)

• Collaboration with SMI

• ……

Parents Prenatal

Perinatal

Childhood Adolescence Adult Aged

Exposure

Outcome

Drug Prescription

Register (WP1)

Multigeneration Register (WP1-WP5)

Inpatient Register (WP1 and WP 3)

Medical Birth

Register (WP1

and WP3)

WP1

•Inpatient

Register (1964-)

•Outpatient

Register (2005-)

•Drug

Prescription

Register (2005-)

•National

Diabetes Register

(1996-)

WP2

•National Crime

Register (1973-)

WP3

Conscript Register (1962-)

Drug Prescription Register (2005-)

WP4

•Inpatient Register (1964-), Outpatient Register

(2005-), RiksSvikt (2003-), SWEDEHEART (1995-),

Riks-Stroke (1994-),Cause of Death Register (1952-)

WP5

•Swedish Cancer Register (1958-), Cause of Death

Register (1952-)

Register of Education (WP3-4)

Population and Housing Censuses 1960 -70 -80 -90 (WP3-WP4)

Sparén P, 2009 Dept. of Medical Epidemiology and Biostatistics 10

Social Mobility Database (Pär

Sparén)

Multi Generation Register

2002

Social Mobility data base

Cancer Register

2006

Patient Register

2005

Causes of Death

Register 2006 Education Register

2002

Medical Birth

Register 2004

Population and Housing

Censuses

1960 1980 1990 1970

Immigrations and

emigrations 2002

~13 m

illi

ons

Sparén P, 2009 Dept. of Medical Epidemiology and Biostatistics 11

Social Mobility Database

Multi Generation Register

2002 2008

Updated Social Mobility data base

Cancer Register

2006 2010

Patient Register

2005 2010

Causes of Death

Register 2006 2010 Education Register

2002 2010

Medical Birth

Register 2004 2010

Population and Housing

Censuses

1960 1980 1990 1970

Immigrations and

emigrations 2002 2008

Sparén P, 2009 Dept. of Medical Epidemiology and Biostatistics 12

Updated Social

Mobility data base

Social Mobility Database

Outpatient data (patient register)

Drug prescription register

Conscription register (men)

Other data sources?

Challenges in data management

1. Data cleaning

2. Standardization of variable names

3. Documentation

4. … …

DBA members:

Ninoa Malki

Åsa Eck

Examples of achievements

WP1 – early life antibiotics exposure

Medical record review for 1952

subjects (out of 2600 randomly

selected, 75%)

250 691

Results: In total, 211 192 children had received prescriptions of antibiotics.

The hazard ratios (HRs) for asthma medication associated with prescription of

Gram-positive infections were stronger (age<=1) HR = 2.27 (95% CI 2.17–2.37)

vs

Urinary tract infections and/or skin and soft tissue infections, (age<=1) HR = 1.04

(0.78–1.40).

Conclusions Our data suggest that the association between antibiotics and

asthma is subject to either reverse causation or confounding by indication due to

respiratory tract infections.

WP2 - adolescent criminality

It was found that although smoking during pregnancy is associated to

obesity, lower intellectual performance, substance use, stress coping,

criminality and all-cause mortality, these association seemed to be

affected by familial factors. This means that the risk are shared by

families through their common such as early environment as well as

their common genes. However, for high blood pressure the association

was shown to be due to maternal smoking during pregnancy.

WP 3 - Prenatal exposures and familial contribution to

young adulthood health - Anastasia Iliadou

WP4 – Familial factors and CVD

• The overall risk of incident ischemic stroke

when exposed was significantly increased

(relative risk, 1.61; 95% CI 1.48 –1.75).

• Familial risk was higher in full (relative risk,

1.64; 95% CI1.50 –1.81) than in half (relative

risk, 1.41; 95% CI 1.10 –1.82 siblings.

• Familial risk of early ischemic stroke almost

doubled when exposed to early ischemic

stroke (relative risk, 1.94; 95% CI 1.41–2.67)

WP5 – cancer familial aggregation

• The highest relative risks were for

same-sex siblings of both female

probands (HR=28.52; 95% CI:

3.43, 237.26) and male probands

(HR=14.60; 95% CI: 5.71, 37.30).

• Sons had a much higher risk than

daughters, especially if the affected

parent was the mother (HR?23.51;

95% CI: 6.92, 79.90)

• Spouses – no increased risk

WP6 – methological development

We developed a unified model for familial risk by extending a Cox

regression model to enable estimation of the detailed effects of

kinship. By appropriate parameterisation of the model, we show how

the risks to all specific first degree kinships can be estimated and

formally compared using simple interaction terms and how the

model can be extended to accommodate higher-degree relatives.

•Vadym Khatsanovskyy, Jan-Eric Litton, Ruslan Fomkin: Improving security by using a

database management system for integrated statistical data analysis. PAIS 2011: 9

•Ruslan Fomkin, Magnus Stenbeck, Jan-Eric Litton: Federated Databases as a Basis for

Infrastructure Supporting Epidemiological Research. DEXA Workshops 2009: 313-317

WP7 – fedeated

database

approach

-

Ruslan Fomkin

Cancer and Parkinson’s disease

PD patients (n = 16,841)

and their siblings

PD patients have

slightly higher cancer risk in general (HR=1.05)

lower risk of smoking-related cancers (HR=0.87)

higher risk of melanoma (HR=1.61)

Siblings of PD patients have

no increased risk of cancer

Interpretation

PD-melanoma association may be due to non-familial

factors

New Initiatives at MEB Node – neuroepidemiology

Wirdefeldt K et al. AJE 2013

Matched cohort (n =

84,205) and their siblings

Cancer incidence

via linkage to

Cancer Register

Other publications in neuroepi theme: Cancer and ALS (Amyotroph Lateral Scler Frontotemporal

Degener., 2013);

Infections and ALS (PLoS One, 2012)

Head trauma and ALS (Amyotroph Lateral Scler

Frontotemporal Degener., 2013);

Head trauma and PD (Mov Disord., 2012);

Infections and PD (Int J Epidemiol., 2012); Overall, a previous cancer diagnosis

was not associated with subsequent

risk of ALS (OR 1.00; 95% CI 0.91 –

1.10).

Conclusions: Our results suggest that acute

and severe infections unlikely contribute to

the development of ALS;

however, ALS patients are at a higher risk of

sepsis after diagnosis, compared to ALS free

individuals.

Suicide and CVD death following a cancer diagnosis

• A cancer diagnosis constitutes a major stressor that instantly affects risks of critical,

fatal outcomes

• Results not confounded by shared etiologies between cancer and suicide/CVD

• Findings highlight the importance of immediate follow-up of newly diagnosed cancer

patients in terms of psychological health and cardiovascular disease

New Initiatives at MEB Node – stress and health

Fang F et al. NEJM 2012

Collaboration with SMI (data can not be exported)

HCV infection might be associated with an increased risk

of pancreatic cancer

Remaining challenges

Still data linkages:

SocMob needs to be reconstructed – data

cleaning again

Next steps:

Extend to underused resources

Thank you