Variants in TF and HFE explain ~40% of genetic variation in serum-transferrin levels

Beben Benyamin, Allan F McRae, Gu Zhu, Scott Gordon, Anjali K Henders, Aarno Palotie, Leena Peltonen, Nicholas G Martin, Grant W Montgomery, John B Whitfield, Peter M Visscher

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

"Only a small proportion of genetic variation in complex traits has been explained by SNPs from genome-wide association studies (GWASs), We report the results from two GWASs for serum markers of iron status (serum iron, serum transferrin, transferrin saturation with iron, and serum ferritin), which are important in iron overload (e.g., hemochromatosis) and deficiency (e.g., anemia) conditions. We performed two GWASs on samples of Australians of European descent. In the first GWAS, 411 adolescent twins and their siblings were genotyped with 100K SNPs. rs1830084, 10.8 kb 3' of TF, was significantly associated with serum transferrin (p total association test = 1.0 x 10(-9); p within-family test = 2.2 x 10(-5)). In the second GWAS on an independent sample of 459 female monozygotic (MZ) twin pairs genotyped with 300K SNPs, we found rs3811647 (within intron 11 of TF, HapMap CEU r(2) with rs1830084 = 0.86) was significantly associated with serum transferrin (p = 3.0 x 10(-1)5). In the second GWAS, we found two additional and independent SNPs on TF (rs1799852 and rs2280673) and confirmed the known C282Y mutation in HFE to be independently associated with serum transferrin. The three variants in TF (rs3811647, rs1799852 and rs2280673) plus the HFE C282Y mutation explained similar to 40% of genetic variation in serum transferrin (p = 7.8 x 10(-25)). These findings are potentially important for our understanding of iron metabolism and of regulation of hepatic protein secretion, and also strongly support the hypothesis that the genetic architecture of some endophenotypes may be simpler than that of disease."
Alkuperäiskielienglanti
LehtiAmerican Journal of Human Genetics
Vuosikerta84
Numero1
Sivut60-65
Sivumäärä6
ISSN0002-9297
DOI - pysyväislinkit
TilaJulkaistu - 2009
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 311 Peruslääketieteet
  • 312 Kliiniset lääketieteet
  • 318 Lääketieteen bioteknologia
  • 217 Lääketieteen tekniikka
  • 118 Biotieteet

Lainaa tätä

Benyamin, Beben ; McRae, Allan F ; Zhu, Gu ; Gordon, Scott ; Henders, Anjali K ; Palotie, Aarno ; Peltonen, Leena ; Martin, Nicholas G ; Montgomery, Grant W ; Whitfield, John B ; Visscher, Peter M. / Variants in TF and HFE explain ~40% of genetic variation in serum-transferrin levels. Julkaisussa: American Journal of Human Genetics. 2009 ; Vuosikerta 84, Nro 1. Sivut 60-65.
@article{b480e4e0fe7640219311a253cda55c49,
title = "Variants in TF and HFE explain ~40{\%} of genetic variation in serum-transferrin levels",
abstract = "{"}Only a small proportion of genetic variation in complex traits has been explained by SNPs from genome-wide association studies (GWASs), We report the results from two GWASs for serum markers of iron status (serum iron, serum transferrin, transferrin saturation with iron, and serum ferritin), which are important in iron overload (e.g., hemochromatosis) and deficiency (e.g., anemia) conditions. We performed two GWASs on samples of Australians of European descent. In the first GWAS, 411 adolescent twins and their siblings were genotyped with 100K SNPs. rs1830084, 10.8 kb 3' of TF, was significantly associated with serum transferrin (p total association test = 1.0 x 10(-9); p within-family test = 2.2 x 10(-5)). In the second GWAS on an independent sample of 459 female monozygotic (MZ) twin pairs genotyped with 300K SNPs, we found rs3811647 (within intron 11 of TF, HapMap CEU r(2) with rs1830084 = 0.86) was significantly associated with serum transferrin (p = 3.0 x 10(-1)5). In the second GWAS, we found two additional and independent SNPs on TF (rs1799852 and rs2280673) and confirmed the known C282Y mutation in HFE to be independently associated with serum transferrin. The three variants in TF (rs3811647, rs1799852 and rs2280673) plus the HFE C282Y mutation explained similar to 40{\%} of genetic variation in serum transferrin (p = 7.8 x 10(-25)). These findings are potentially important for our understanding of iron metabolism and of regulation of hepatic protein secretion, and also strongly support the hypothesis that the genetic architecture of some endophenotypes may be simpler than that of disease.{"}",
keywords = "311 Basic medicine, 312 Clinical medicine, 318 Medical biotechnology, 217 Medical engineering, 118 Biological sciences",
author = "Beben Benyamin and McRae, {Allan F} and Gu Zhu and Scott Gordon and Henders, {Anjali K} and Aarno Palotie and Leena Peltonen and Martin, {Nicholas G} and Montgomery, {Grant W} and Whitfield, {John B} and Visscher, {Peter M}",
year = "2009",
doi = "10.1016/j.ajhg.2008.11.011",
language = "English",
volume = "84",
pages = "60--65",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "1",

}

Benyamin, B, McRae, AF, Zhu, G, Gordon, S, Henders, AK, Palotie, A, Peltonen, L, Martin, NG, Montgomery, GW, Whitfield, JB & Visscher, PM 2009, 'Variants in TF and HFE explain ~40% of genetic variation in serum-transferrin levels', American Journal of Human Genetics, Vuosikerta 84, Nro 1, Sivut 60-65. https://doi.org/10.1016/j.ajhg.2008.11.011

Variants in TF and HFE explain ~40% of genetic variation in serum-transferrin levels. / Benyamin, Beben; McRae, Allan F; Zhu, Gu; Gordon, Scott; Henders, Anjali K; Palotie, Aarno; Peltonen, Leena; Martin, Nicholas G; Montgomery, Grant W; Whitfield, John B; Visscher, Peter M.

julkaisussa: American Journal of Human Genetics, Vuosikerta 84, Nro 1, 2009, s. 60-65.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Variants in TF and HFE explain ~40% of genetic variation in serum-transferrin levels

AU - Benyamin, Beben

AU - McRae, Allan F

AU - Zhu, Gu

AU - Gordon, Scott

AU - Henders, Anjali K

AU - Palotie, Aarno

AU - Peltonen, Leena

AU - Martin, Nicholas G

AU - Montgomery, Grant W

AU - Whitfield, John B

AU - Visscher, Peter M

PY - 2009

Y1 - 2009

N2 - "Only a small proportion of genetic variation in complex traits has been explained by SNPs from genome-wide association studies (GWASs), We report the results from two GWASs for serum markers of iron status (serum iron, serum transferrin, transferrin saturation with iron, and serum ferritin), which are important in iron overload (e.g., hemochromatosis) and deficiency (e.g., anemia) conditions. We performed two GWASs on samples of Australians of European descent. In the first GWAS, 411 adolescent twins and their siblings were genotyped with 100K SNPs. rs1830084, 10.8 kb 3' of TF, was significantly associated with serum transferrin (p total association test = 1.0 x 10(-9); p within-family test = 2.2 x 10(-5)). In the second GWAS on an independent sample of 459 female monozygotic (MZ) twin pairs genotyped with 300K SNPs, we found rs3811647 (within intron 11 of TF, HapMap CEU r(2) with rs1830084 = 0.86) was significantly associated with serum transferrin (p = 3.0 x 10(-1)5). In the second GWAS, we found two additional and independent SNPs on TF (rs1799852 and rs2280673) and confirmed the known C282Y mutation in HFE to be independently associated with serum transferrin. The three variants in TF (rs3811647, rs1799852 and rs2280673) plus the HFE C282Y mutation explained similar to 40% of genetic variation in serum transferrin (p = 7.8 x 10(-25)). These findings are potentially important for our understanding of iron metabolism and of regulation of hepatic protein secretion, and also strongly support the hypothesis that the genetic architecture of some endophenotypes may be simpler than that of disease."

AB - "Only a small proportion of genetic variation in complex traits has been explained by SNPs from genome-wide association studies (GWASs), We report the results from two GWASs for serum markers of iron status (serum iron, serum transferrin, transferrin saturation with iron, and serum ferritin), which are important in iron overload (e.g., hemochromatosis) and deficiency (e.g., anemia) conditions. We performed two GWASs on samples of Australians of European descent. In the first GWAS, 411 adolescent twins and their siblings were genotyped with 100K SNPs. rs1830084, 10.8 kb 3' of TF, was significantly associated with serum transferrin (p total association test = 1.0 x 10(-9); p within-family test = 2.2 x 10(-5)). In the second GWAS on an independent sample of 459 female monozygotic (MZ) twin pairs genotyped with 300K SNPs, we found rs3811647 (within intron 11 of TF, HapMap CEU r(2) with rs1830084 = 0.86) was significantly associated with serum transferrin (p = 3.0 x 10(-1)5). In the second GWAS, we found two additional and independent SNPs on TF (rs1799852 and rs2280673) and confirmed the known C282Y mutation in HFE to be independently associated with serum transferrin. The three variants in TF (rs3811647, rs1799852 and rs2280673) plus the HFE C282Y mutation explained similar to 40% of genetic variation in serum transferrin (p = 7.8 x 10(-25)). These findings are potentially important for our understanding of iron metabolism and of regulation of hepatic protein secretion, and also strongly support the hypothesis that the genetic architecture of some endophenotypes may be simpler than that of disease."

KW - 311 Basic medicine

KW - 312 Clinical medicine

KW - 318 Medical biotechnology

KW - 217 Medical engineering

KW - 118 Biological sciences

U2 - 10.1016/j.ajhg.2008.11.011

DO - 10.1016/j.ajhg.2008.11.011

M3 - Article

VL - 84

SP - 60

EP - 65

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 1

ER -