Anaemia is a major determinant of global ill-health, contributing to cognitive impairment, growth retardation, and impaired physical capacity.1 To increase knowledge of the genetic factors influencing red blood cells we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. We identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P<10-8, which together explain 4-9% of the phenotypic variance per trait. Using expression QTL and bioinformatic strategies we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are preferentially expressed in red blood cell precursors, and 43 have haematopoietic phenotypes in M. musculus or D. melanogaster. Through open chromatin and coding variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
75 genetic loci influencing the human red blood cell
DANJOU, FABRICE;ANNI, FRANCO;
2012-01-01
Abstract
Anaemia is a major determinant of global ill-health, contributing to cognitive impairment, growth retardation, and impaired physical capacity.1 To increase knowledge of the genetic factors influencing red blood cells we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. We identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P<10-8, which together explain 4-9% of the phenotypic variance per trait. Using expression QTL and bioinformatic strategies we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are preferentially expressed in red blood cell precursors, and 43 have haematopoietic phenotypes in M. musculus or D. melanogaster. Through open chromatin and coding variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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