Genome wide association study of fetal hemoglobin in sickle cell Anemia in Tanzania

Siana Nkya Mtatiro; Tarjinder Singh; Helen Rooks; Josephine Mgaya; Harvest Mariki; Deogratius Soka; Bruno Mmbando; Evarist Msaki; Iris Kolder; Swee Lay Thein; Stephan Menzel; Sharon E. Cox; Julie Makani; Jeffrey C. Barrett

doi:10.1371/journal.pone.0111464

Genome wide association study of fetal hemoglobin in sickle cell Anemia in Tanzania

Siana Nkya Mtatiro^*, Tarjinder Singh, Helen Rooks, Josephine Mgaya, Harvest Mariki, Deogratius Soka, Bruno Mmbando, Evarist Msaki, Iris Kolder, Swee Lay Thein, Stephan Menzel, Sharon E. Cox, Julie Makani, Jeffrey C. Barrett

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Fetal hemoglobin (HbF) is an important modulator of sickle cell disease (SCD). HbF has previously been shown to be affected by variants at three loci on chromosomes 2, 6 and 11, but it is likely that additional loci remain to be discovered.

Methods and Findings: We conducted a genome-wide association study (GWAS) in 1,213 SCA (HbSS/HbSβ0) patients in Tanzania. Genotyping was done with Illumina Omni2.5 array and imputation using 1000 Genomes Phase I release data. Association with HbF was analysed using a linear mixed model to control for complex population structure within our study. We successfully replicated known associations for HbF near BCL11A and the HBS1L-MYB intergenic polymorphisms (HMIP), including multiple independent effects near BCL11A, consistent with previous reports. We observed eight additional associations with P

Conclusions: This is the largest GWAS study in SCA in Africa. We have confirmed known associations and identified new genetic associations with HbF that require further replication in SCA populations in Africa.

Original language	English
Article number	e111464
Journal	PL o S One
Volume	9
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0111464
Publication status	Published - 5 Nov 2014

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title = "Genome wide association study of fetal hemoglobin in sickle cell Anemia in Tanzania",

abstract = "Background: Fetal hemoglobin (HbF) is an important modulator of sickle cell disease (SCD). HbF has previously been shown to be affected by variants at three loci on chromosomes 2, 6 and 11, but it is likely that additional loci remain to be discovered.Methods and Findings: We conducted a genome-wide association study (GWAS) in 1,213 SCA (HbSS/HbSβ0) patients in Tanzania. Genotyping was done with Illumina Omni2.5 array and imputation using 1000 Genomes Phase I release data. Association with HbF was analysed using a linear mixed model to control for complex population structure within our study. We successfully replicated known associations for HbF near BCL11A and the HBS1L-MYB intergenic polymorphisms (HMIP), including multiple independent effects near BCL11A, consistent with previous reports. We observed eight additional associations with PConclusions: This is the largest GWAS study in SCA in Africa. We have confirmed known associations and identified new genetic associations with HbF that require further replication in SCA populations in Africa.",

author = "Mtatiro, {Siana Nkya} and Tarjinder Singh and Helen Rooks and Josephine Mgaya and Harvest Mariki and Deogratius Soka and Bruno Mmbando and Evarist Msaki and Iris Kolder and Thein, {Swee Lay} and Stephan Menzel and Cox, {Sharon E.} and Julie Makani and Barrett, {Jeffrey C.}",

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T1 - Genome wide association study of fetal hemoglobin in sickle cell Anemia in Tanzania

AU - Mtatiro, Siana Nkya

AU - Singh, Tarjinder

AU - Rooks, Helen

AU - Mgaya, Josephine

AU - Mariki, Harvest

AU - Soka, Deogratius

AU - Mmbando, Bruno

AU - Msaki, Evarist

AU - Kolder, Iris

AU - Thein, Swee Lay

AU - Menzel, Stephan

AU - Cox, Sharon E.

AU - Makani, Julie

AU - Barrett, Jeffrey C.

PY - 2014/11/5

Y1 - 2014/11/5

N2 - Background: Fetal hemoglobin (HbF) is an important modulator of sickle cell disease (SCD). HbF has previously been shown to be affected by variants at three loci on chromosomes 2, 6 and 11, but it is likely that additional loci remain to be discovered.Methods and Findings: We conducted a genome-wide association study (GWAS) in 1,213 SCA (HbSS/HbSβ0) patients in Tanzania. Genotyping was done with Illumina Omni2.5 array and imputation using 1000 Genomes Phase I release data. Association with HbF was analysed using a linear mixed model to control for complex population structure within our study. We successfully replicated known associations for HbF near BCL11A and the HBS1L-MYB intergenic polymorphisms (HMIP), including multiple independent effects near BCL11A, consistent with previous reports. We observed eight additional associations with PConclusions: This is the largest GWAS study in SCA in Africa. We have confirmed known associations and identified new genetic associations with HbF that require further replication in SCA populations in Africa.

AB - Background: Fetal hemoglobin (HbF) is an important modulator of sickle cell disease (SCD). HbF has previously been shown to be affected by variants at three loci on chromosomes 2, 6 and 11, but it is likely that additional loci remain to be discovered.Methods and Findings: We conducted a genome-wide association study (GWAS) in 1,213 SCA (HbSS/HbSβ0) patients in Tanzania. Genotyping was done with Illumina Omni2.5 array and imputation using 1000 Genomes Phase I release data. Association with HbF was analysed using a linear mixed model to control for complex population structure within our study. We successfully replicated known associations for HbF near BCL11A and the HBS1L-MYB intergenic polymorphisms (HMIP), including multiple independent effects near BCL11A, consistent with previous reports. We observed eight additional associations with PConclusions: This is the largest GWAS study in SCA in Africa. We have confirmed known associations and identified new genetic associations with HbF that require further replication in SCA populations in Africa.

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Genome wide association study of fetal hemoglobin in sickle cell Anemia in Tanzania

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