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

Nat Genet. 2015 Nov;47(11):1264-71. doi: 10.1038/ng.3307. Epub 2015 Sep 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Genetic Variation
  • Genome, Human / genetics*
  • Genome-Wide Association Study / methods*
  • Genotype
  • Genotyping Techniques / methods*
  • Hemoglobins / genetics*
  • Humans
  • Islands
  • Italy
  • Male
  • Middle Aged
  • Multigene Family
  • Polymorphism, Single Nucleotide
  • Sequence Analysis, DNA / methods*
  • alpha-Globins / genetics
  • beta-Globins / genetics

Substances

  • Hemoglobins
  • alpha-Globins
  • beta-Globins