Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels

Fabrice Danjou; Magdalena Zoledziewska; Carlo Sidore; Maristella Steri; Fabio Busonero; Andrea Maschio; Antonella Mulas; Lucia Perseu; Susanna Barella; Eleonora Porcu; Giorgio Pistis; Maristella Pitzalis; Mauro Pala; Stephan Menzel; Sarah Metrustry; Timothy D Spector; Lidia Leoni; Andrea Angius; Manuela Uda; Paolo Moi; Swee Lay Thein; Renzo Galanello; Gonçalo R Abecasis; David Schlessinger; Serena Sanna; Francesco Cucca

doi:10.1038/ng.3307

Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels

Fabrice Danjou, Magdalena Zoledziewska, Carlo Sidore, Maristella Steri, Fabio Busonero, Andrea Maschio, Antonella Mulas, Lucia Perseu, Susanna Barella, Eleonora Porcu, Giorgio Pistis, Maristella Pitzalis, Mauro Pala, Stephan Menzel, Sarah Metrustry, Timothy D Spector, Lidia Leoni, Andrea Angius, Manuela Uda, Paolo MoiSwee Lay Thein, Renzo Galanello, Gonçalo R Abecasis, David Schlessinger, Serena Sanna, Francesco Cucca

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Abstract

We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.

Original language	English
Pages (from-to)	1264–1271
Journal	Nature Genetics
Volume	47
Issue number	11
Early online date	14 Sept 2015
DOIs	https://doi.org/10.1038/ng.3307
Publication status	Published - 1 Nov 2015

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Genome-wide association analyses_DANJOU_Accepted 23Apr2015_GREEN AAMAccepted author manuscript, 1.52 MB

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Danjou, F., Zoledziewska, M., Sidore, C., Steri, M., Busonero, F., Maschio, A., Mulas, A., Perseu, L., Barella, S., Porcu, E., Pistis, G., Pitzalis, M., Pala, M., Menzel, S., Metrustry, S., Spector, T. D., Leoni, L., Angius, A., Uda, M., ... Cucca, F. (2015). Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels. Nature Genetics, 47(11), 1264–1271. https://doi.org/10.1038/ng.3307

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title = "Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels",

abstract = "We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.",

author = "Fabrice Danjou and Magdalena Zoledziewska and Carlo Sidore and Maristella Steri and Fabio Busonero and Andrea Maschio and Antonella Mulas and Lucia Perseu and Susanna Barella and Eleonora Porcu and Giorgio Pistis and Maristella Pitzalis and Mauro Pala and Stephan Menzel and Sarah Metrustry and Spector, {Timothy D} and Lidia Leoni and Andrea Angius and Manuela Uda and Paolo Moi and Thein, {Swee Lay} and Renzo Galanello and Abecasis, {Gon{\c c}alo R} and David Schlessinger and Serena Sanna and Francesco Cucca",

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doi = "10.1038/ng.3307",

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Danjou, F, Zoledziewska, M, Sidore, C, Steri, M, Busonero, F, Maschio, A, Mulas, A, Perseu, L, Barella, S, Porcu, E, Pistis, G, Pitzalis, M, Pala, M, Menzel, S , Metrustry, S , Spector, TD, Leoni, L, Angius, A, Uda, M, Moi, P, Thein, SL, Galanello, R, Abecasis, GR, Schlessinger, D, Sanna, S & Cucca, F 2015, 'Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels', Nature Genetics, vol. 47, no. 11, pp. 1264–1271. https://doi.org/10.1038/ng.3307

TY - JOUR

T1 - Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels

AU - Danjou, Fabrice

AU - Zoledziewska, Magdalena

AU - Sidore, Carlo

AU - Steri, Maristella

AU - Busonero, Fabio

AU - Maschio, Andrea

AU - Mulas, Antonella

AU - Perseu, Lucia

AU - Barella, Susanna

AU - Porcu, Eleonora

AU - Pistis, Giorgio

AU - Pitzalis, Maristella

AU - Pala, Mauro

AU - Menzel, Stephan

AU - Metrustry, Sarah

AU - Spector, Timothy D

AU - Leoni, Lidia

AU - Angius, Andrea

AU - Uda, Manuela

AU - Moi, Paolo

AU - Thein, Swee Lay

AU - Galanello, Renzo

AU - Abecasis, Gonçalo R

AU - Schlessinger, David

AU - Sanna, Serena

AU - Cucca, Francesco

PY - 2015/11/1

Y1 - 2015/11/1

N2 - We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.

AB - We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.

U2 - 10.1038/ng.3307

DO - 10.1038/ng.3307

M3 - Article

C2 - 26366553

SN - 1061-4036

VL - 47

SP - 1264

EP - 1271

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels

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