PAGES is a study trying to understand the genetic and environmental factors explaining the risk of Autism Spectrum Disorder (ASD). The purpose is to find specific genes and potential environmental factors that affect the risk of developing Autistic Disorder, Asperger or Atypical autism.

"PAGES" is an abbreviation for “Population-Based Autism Genetics and Environmental Study”, which illustrates that it is not only a single gene that leads to an increased risk of autism but a complex pattern of several different genes and environmental factors, which in combination creates increased vulnerability. The PAGES study is a collaboration between Karolinska Institutet and the Seaver Autism Center for Research and Treatment at the Icahn School of Medicine in New York, USA, one of the world's leading research institutes for autism research. Most of the funding comes from the USA, from national research grants, but also from donations from people who want to help to promote research on autism spectrum states.

What is Autism Spectrum Disorder?

ASD is a disorder that affects at least 1% of all children and adolescents in Sweden. The first signs of ASD are typically seen during early pre-school age and are characterized by communication problems and difficulty to interpret and understand other people's thoughts and feelings.
Both genes and the environment are important causes for ASD. Research from our group using collected genetic material has previously shown that genes are of importance. There are most likely many genes involved in the development of autism and these probably affect the production and absorption of important proteins in the brain cells. An increased sensitivity in these systems may increase the risk of ASD, especially in combination with external stresses and environmental factors. More information about ASD can be found here on the 1177 Care Advisory website or on the Autism & Asperger Federation website.

Study information

About 1 in 100 are diagnosed with ASD at some point in life. It has long been assumed that ASD is inherited in the family. In recent years, family studies using knowledge about the genetic relationship between different family members have shown that the variation in risk that can be explained by genetic factors is about 80% (this measure is commonly referred to as "heritability"). Previously collected genetic material (blood and saliva samples) from Karolinska Institutet has also played an important role. We have also been able to demonstrate the high heredity through genetic data.

The causes of autism spectrum states appear to be genetically complex. A large number of genes, each with only a modest effect individually, when acting together can cause a vulnerability and can, together with environmental factors, trigger the ASD.

In recent years, the techniques for genetic studies of complex diseases have developed rapidly. Through genome-wide association studies (GWAS), several vulnerabilities have been identified for type 1 and 2 diabetes, rheumatism, cardiovascular disease, prostate and breast cancer, for example. This has been of great importance for understanding the mechanisms of these diseases. For ASD, several studies have been conducted with promising results that form the basis for further studies, but the findings of these studies have not been possible to be replicated. To move the research in psychiatric genetics forward and close the gaps in knowledge, large and well-defined studies are needed. Using the large Swedish state-of-the-art registers of the Swedish government National Board of Health and Welfare, we have a unique opportunity to achieve these goals.


In our study we invite people born in Sweden and who have been diagnosed with ASD at some point during their lives. When we invite people to participate in the study, we only have information that the person has been diagnosed with autism at some point in life. We have no data from medical records, current health or any other diagnoses. Information about an autism diagnosis comes from the Patient Register, held by the National Board of Health and Welfare. This is a health register for both somatic and psychiatric diagnoses and contains all psychiatric care facilities in Sweden from 1973 and onwards, and to a varying degree, also includes out-patient care. Only clinical specialists may assign an autism diagnosis that is stored in the Patient Register.

The participants are invited through an information letter followed by a telephone call from one of our research nurses. Since people with autism sometimes can be difficult to reach, we try to work with relatives, close relatives and treatment staff when needed. Individuals with autism may exhibit a varying degree of symptoms. For the most severely affected, we have developed a picture support in addition to the information sent to the invited persons, which explains the examination procedure in a simple way, thus increasing the chance that everyone will be able to decide if they want to participate in the study or not.

If the person decides to participate, we first require a signed consent that the person wishes to participate in the study. The person is then asked to give a saliva sample. Sometimes people may have problems with a dry mouth, but we only ask for a small amount of saliva, about 2 ml. If the participant so wishes, it is possible to give a blood sample instead of a saliva sample. All participants are also asked if we can obtain information about them from other national registries, such as the Medical Birth Register, the National Patient Registry, the Multi-Generation Register and the Prescription Register. The purpose is to enable linkage between genetic data and other characteristics of the participants. Examples of such information are the age of the mother and the father when the person was born. The age of parents has been shown to be of importance for developing ASD in several research studies, and it is therefore important to be able to study whether genetic markers can provide any information to better understand these relationships.

When data collection is complete and all analyzes are complete, comparisons will be made to investigate whether genetic variants appear to be more vulnerable to the development of ASD. The group of people with ASD will be compared with control persons who do not have an ASD diagnosis. Processing of the data will be performed without identifying individual persons.

Significance and purpose

The PAGES study is unique in its kind as it is a national population-based study. This means that we request information from all living in a certain geographical area. Using this approach we can avoid many problems when interpreting research findings that may occur if a smaller group of individuals is included. Our research group has experience of conducting similar studies on Obsessive-Compulsive Disorder (EGOs), Schizophrenia (BROAD study) and bipolar disorder (STANLEY study). Since ASD may share certain genetic causative factors with schizophrenia and other psychotic diseases, the overall results of these studies can provide important information and increased understanding of underlying factors.

What is happening in the study?

In October 2018, we will send out the first study invitations. We will then continue recruitment for at least three years. We will update our website continuously to inform about how the study develops and when we publish research findings that are relevant to the study or that use data that our participants have contributed.

In February 2019, we have published a new scientific article in Nature. In this study where genetic data from PAGES were included, for the first time, 12 common gene variants that increase the risk of autism were discovered.

What's the importance of participating in the study?

Participating in a scientific study does not always directly benefit the person involved but the participation can be of major significance to other people who suffer from the same disability or disease, both in our own generation and in future generations, in Sweden as well as internationally. In particular, the understanding of the causes of these conditions can help prevent both the development of ill health and disease and improve treatment.

Participation in the study is entirely voluntary. The participant may, at any time, suspend his participation and by law (GDPR) request that all collected information be deleted.

What happens to the sample?

Each person participating in the study gives a saliva sample of about 2 ml. The samples are sent to the Karolinska Institutet Biobank where DNA (legacy) is extracted. A subset of the sample is then sent to a genetic laboratory where genetic analyzes are performed. When data collection is complete and all analyzes are complete, comparisons will be made to investigate whether genetic variants appear to be more vulnerable to the development of ASD. Processing of the data will be performed without identifying individuals. Results will always be reported at group level.


The samples will be stored in Karolinska Institutet biobank. Since 2003, there has been a Swedish law on biobanks, the Biobanks Act (BbL 2002: 297), which means that the participant will get information about and approve that samples are stored in a biobank and what they may be used for. The person who has provided a sample also must decide on how the samples may be used in the future. You are always entitled to change your decision at any time.

Research and Ethics

According to Swedish law (Ethics Examination Act - Law 2003: 460) on ethics testing of human-related research), all research projects must be approved by a research ethics committee that assesses whether the project is important and whether it can be implemented without compromising the integrity of the study participant. This study has received such approval by the Regional Ethics Vetting Board in Stockholm. All personal data and samples are protected.

Saved samples are stored with unique codes so that unauthorized users cannot access them. Personal data is protected under the Data Protection Regulation (GDPR), which applies throughout the EU. You can request in writing to find out what data is registered about yourself. Once a year you are is entitled to order such an excerpt without charge. You also have the right to change information about yourself that is incorrect or incorrectly processed.

Responsible for the data register in the study is Karolinska Institutet, 171 77 Stockholm, tel. 08-524 800 00. Head of the study is research leader Sven Sandin, tel. 08-524 861 22 and Professor Christina Hultman; both belonging to the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet Solna.

Study personnel

Profile image

Sven Sandin



The information and data provided by our study participants have already resulted in a number of scientific papers published in highly ranked international scientific journals. See the list below for some examples. All these studies are available to the general public so anyone can read them, so called open access. Naturally there is no information about individuals reported in the papers, but all information is reported on a group level.

Identification of common genetic risk variants for autism spectrum disorder.
Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, et al
Nat. Genet. 2019 03;51(3):431-444

The Heritability of Autism Spectrum Disorder.
Sandin S, Lichtenstein P, Kuja-Halkola R, Hultman C, Larsson H, Reichenberg A
JAMA 2017 09;318(12):1182-1184

Most genetic risk for autism resides with common variation.
Gaugler T, Klei L, Sanders SJ, Bodea CA, Goldberg AP, Lee AB, et al
Nat. Genet. 2014 Aug;46(8):881-5

Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.
Sanders SJ, He X, Willsey AJ, Ercan-Sencicek AG, Samocha KE, Cicek AE, et al
Neuron 2015 Sep;87(6):1215-1233

Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.
Lim ET, Uddin M, De Rubeis S, Chan Y, Kamumbu AS, Zhang X, et al
Nat. Neurosci. 2017 09;20(9):1217-1224

Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

Mol Autism 2017 ;8():21

Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K, Cicek AE, et al
Nature 2014 Nov;515(7526):209-15

Common risk variants identified in autism spectrum disorder. Grove J, Ripke S, Als TD, et al. bioRxiv 2017;:224774.

ASD and ADHD have a similar burden of rare protein-truncating variants. Satterstrom FK, Walters RK, Singh T, et al. bioRxiv 2018;:277707.

Analysis of shared heritability in common disorders of the brain.
Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, et al
Science 2018 06;360(6395):

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