biostudies-literatureOrru VIntramural NIH HHSNIDA NIH HHSNIA NIH HHSNHGRI NIH HHS242-56https://www.ebi.ac.uk/biostudies/studies/S-EPMC5541764biostudies-literatureUnknown155(1)The complex network of specialized cells and molecules in the immune system has evolved to defend against pathogens, but inadvertent immune system attacks on "self" result in autoimmune disease. Both genetic regulation of immune cell levels and their relationships with autoimmunity are largely undetermined. Here, we report genetic contributions to quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages. We first estimated trait heritability, showing that it can be substantial, accounting for up to 87% of the variance (mean 41%). Next, by assessing ∼8.2 million variants that we identified and confirmed in an extended set of 2,870 individuals, 23 independent variants at 13 loci associated with at least one tCellGenetic variants regulating immune cell levels in health and disease.PMC5541764ZIA AG000675HG006513U01 HG006513RC2 HG005552HG005552N01-AG-1-2109HHSN271201100005CRC2 HG005581HG005581HG007022R01 HG007022Firinu DBusonero FMaschio AAbecasis GRSanna SPiras MGUrru MFZoledziewska MWhalen MBOlla SReinier FAtzeni RPireddu LPorcu ESerra VLeoni LCucca FKang HMLobina MSole GKwong AFiorillo EFloris MBrennan CUzzau SLyons RValentini MOppo MTarrier BRotta GPitzalis MSchlessinger DUrru SAVirdis FDeidda FCongia MMarcelli MPilu RJones CMMulas ASidore CMarongiu MSteri MBerutti RAngius AOrru VMentzen WIDei MNaitza SLai SCusano RZara IfalseGenetic variants regulating immune cell levels in health and disease.The complex network of specialized cells and molecules in the immune system has evolved to defend against pathogens, but inadvertent immune system attacks on "self" result in autoimmune disease. Both genetic regulation of immune cell levels and their relationships with autoimmunity are largely undetermined. Here, we report genetic contributions to quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages. We first estimated trait heritability, showing that it can be substantial, accounting for up to 87% of the variance (mean 41%). Next, by assessing ∼8.2 million variants that we identified and confirmed in an extended set of 2,870 individuals, 23 independent variants at 13 loci associated with at least one t2013-01-01T00:00:00Z2013 Sep2026-04-29T06:44:09.51Z2019-03-27T02:52:32ZS-EPMC55417642407487210.1016/j.cell.2013.08.041