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Consortial Project 1

Started 2005

Human
 

Introduction

Consortial Project 1 investigated human genetic factors involved in resistance to severe malaria in order to better understand why, in regions where people are repeatedly exposed to malaria parasites, some people die from the infection while others survive.

Objectives & Coordination

Investigating the genetic determinants of resistance to malaria

A person’s risk of developing severe malaria is influenced by many different genetic and environmental factors, but we know relatively little about their precise nature and how they interact.

This project’s primary objective was to better understand the human genetic factors involved in resistance to severe malaria. This information could provide vital clues about molecular mechanisms of protective immunity and host-parasite interactions, as well as accelerate the development of an effective vaccine.

There are many aspects to our work:

  • Leading research into the ethical issues inherit in these studies, for example informed consent, and data-sharing in low- and middle-income countries
  • Working with our partner studies to support the necessary clinical research infrastructure to gather standardised samples from many thousands of individuals in several malaria-endemic countries in Africa
  • Generating a large and unique data resource for case-control and family-based studies of genetic resistance and susceptibility to severe malaria
  • Developing methods to overcome the unique challenges confronting multi-centre genome-wide association studies (GWAS) in Africa, for example higher levels of genetic diversity, ethnic diversity, and population structure in Africa than on other continents
  • Supporting capacity building for genetic and genomic research amongst scientists in malaria-endemic countries.

This project began shortly after MalariaGEN was formed in 2005, and has greatly influenced our approach to collaborative science.

Locations

Across the different partner studies, samples were collected from 11,890 children and adults with severe P. falciparum malaria and 17,441 healthy controls matched with the cases by ethnic group, providing a unique resource for case-control and family-based studies.

Sampling locations

Burkina Faso, Cameroon, The Gambia, Ghana, Kenya, Malawi, Mali, Nigeria, Papua New Guinea, Tanzania, Vietnam.

Data

The MalariaGEN human consortial projects have produced substantial data resources and collectively agreed to a managed access mechanism for releasing Human GWAS data sets.

For information on how to apply for access, see Human GWAS data.

Current

Host-parasite interactions: P. falciparum genome sequencing and genotypes from severe malaria cases

Host-parasite interaction using over 4,000 DNA samples from children confirmed to have severe malaria in the period 1995-2009 to test for association between human and P.falciparum genetic variants.

Terms of use

Genome-wide study of resistance to severe malaria in eleven populations (version 2)

Genome-wide genotype data for 10,792 severe malaria- affected individuals and 10,063 controls from eleven worldwide populations; and direct typing of selected genetic variants in 15,865 severe malaria-affected individuals and 19,845 controls from the same populations.

Apply for access to
Human GWAS data

Genome-wide study of resistance to severe malaria in eleven populations (version 1)

EGA Study ID: EGAS00001001311

Three populations: Gambia (2,786 controls; 2,807 cases; 1 parents); Kenya (1,708 controls; 1,944 cases; 180 parents; 33 other); Malawi (1,498 controls; 1,590 cases)

Apply for access to
Human GWAS data

Archived

Imputation-based meta-analysis of severe malaria

EGA Study ID: EGAS00001000807

Three populations: Gambia (1,533 controls; 1,247 cases); Kenya (1,544 controls; 1,711 cases); Malawi (2,239 controls; 1,451 cases)

Apply for access to
Human GWAS data

Archived

Gambia Case-Control Study

EGA Study ID: EGAS00000000026

EGA Data Set IDs: EGAD00000000017 (1,496 controls); EGAD00000000018 (1,059 cases)

Method: Affymetrix 500K array

Apply for access to
Human GWAS data

Archived

Gambia, Ghana, and Malawi Trios

EGA Study IDs: EGAS00000000087 (Gambia); EGAS00000000088 (Ghana)

Three populations: Gambia (658 trios; 1,984 individuals); Ghana (608 trios; 1,824 individuals); Malawi (122 trios; 366 individuals)
Method: Illumina 650Y array

Apply for access to
Human GWAS data

Partner studies

We worked with investigators who pursued independent partner studies in a number of malaria-endemic countries.

A case-control approach to the identification of polymorphisms associated with severe malaria in Kilifi, Kenya

About this study Summary Study site description Methods Ethics Additional contributors Acknowledgements Key people Malaria is a leading cause of death in much of sub-Saharan Africa (World Health Organization, 2008). Host genetic factors…

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Human genetic determinants of severe Plasmodium falciparum malaria in Vietnam

About this study Summary Study site description Methods Ethics Additional contributors Acknowledgements Key people The last decade has seen a decline in the number of reported malaria cases in Vietnam from 187,994 in…

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Human genetic determinants of severe malaria in Burkina Faso

About this study Summary Study site description Methods Ethics Additional contributors Acknowledgements Key people Severe malaria is a life-threatening disease that kills over a million individuals every year, with 90% of the deaths…

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Human genetic determinants of severe malaria in Kumasi, Ghana

About this study Summary Study site description Methods Ethics Additional contributors Acknowledgements Key people Severe malaria, caused by infection with Plasmodium falciparum, remains one of the major health problems in sub-Saharan Africa (World…

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Human genetic determinants of severe malaria in Malawi

About this study Summary Study site description Methods Ethics Additional contributors Acknowledgements Key people Plasmodium falciparum malaria has been identified as the cause of 30-40% of paediatric hospital attendances and up to 30%…

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Human genetic determinants of severe malaria in Mali

About this study Summary Study site description Methods Ethics Additional contributors Acknowledgements Key people Malaria is a life-threatening parasitic disease transmitted by Anopheles mosquitoes. Despite major efforts to control the disease, it still…

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Human genetic determinants of severe malaria in Nigeria

About this study Summary Study site description Methods Ethics Additional contributors Acknowledgements Key people Malaria remains one of the leading causes of morbidity and mortality in malaria endemic regions of the world. The…

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Human genetic determinants of severe malaria in North East Tanzania

About this study Summary Study site description Methods Ethics Additional contributors Acknowledgements Key people Malaria is known to be a strong factor for selection of human genes that give protection against the disease.…

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Human genetic determinants of severe malaria in Papua New Guinea

About this study Summary Study site description Methods Ethics Additional contributors Acknowledgements Key people The populations of the South West Pacific are highly diverse and exhibit a range of red blood cell (RBC)…

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Human genetic determinants of severe malaria in The Gambia

About this study Summary Study site description Methods Ethics Additional contributors Acknowledgements Key people Genetic factors play an important role in resistance to malaria infection but many of the genes responsible remain unknown.…

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Human genetic determinants of severe malaria in the Kassena-Nankana District of Northern Ghana

About this study Summary Study site description Methods Ethics Additional contributors Acknowledgements Key people Malaria, caused by the parasite Plasmodium falciparum, remains the most important disease in sub-Saharan Africa and a leading cause…

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Human genetic determinants of severe malaria in three regions of Cameroon

About this study Summary Study site description Methods Ethics Additional contributors Acknowledgements Key people Malaria remains one of the most widespread infectious diseases of humankind, causing debilitating illness in hundreds of millions of…

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Publications