PMID- 22595970
OWN - NLM
STAT- MEDLINE
DCOM- 20130206
LR  - 20211021
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 21
IP  - 16
DP  - 2012 Aug 15
TI  - Identification of cis-regulatory variation influencing protein abundance levels 
      in human plasma.
PG  - 3719-26
AB  - Proteins are central to almost all cellular processes, and dysregulation of 
      expression and function is associated with a range of disorders. A number of 
      studies in human have recently shown that genetic factors significantly 
      contribute gene expression variation. In contrast, very little is known about the 
      genetic basis of variation in protein abundance in man. Here, we assayed the 
      abundance levels of proteins in plasma from 96 elderly Europeans using a new 
      aptamer-based proteomic technology and performed genome-wide local (cis-) 
      regulatory association analysis to identify protein quantitative trait loci 
      (pQTL). We detected robust cis-associations for 60 proteins at a false discovery 
      rate of 5%. The most highly significant single nucleotide polymorphism detected 
      was rs7021589 (false discovery rate, 2.5 x 10(-12)), mapped within the gene 
      coding sequence of Tenascin C (TNC). Importantly, we identified evidence of 
      cis-regulatory variation for 20 previously disease-associated genes encoding 
      protein, including variants with strong evidence of disease association show 
      significant association with protein abundance levels. These results demonstrate 
      that common genetic variants contribute to the differences in protein abundance 
      levels in human plasma. Identification of pQTLs will significantly enhance our 
      ability to discover and comprehend the biological and functional consequences of 
      loci identified from genome-wide association study of complex traits. This is the 
      first large-scale genetic association study of proteins in plasma measured using 
      a novel, highly multiplexed slow off-rate modified aptamer (SOMAmer) proteomic 
      platform.
FAU - Lourdusamy, Anbarasu
AU  - Lourdusamy A
AD  - NIHR Biomedical Research Centre for Mental Health, South London, UK. 
      anbarasu.lourdusamy@kcl.ac.uk
FAU - Newhouse, Stephan
AU  - Newhouse S
FAU - Lunnon, Katie
AU  - Lunnon K
FAU - Proitsi, Petra
AU  - Proitsi P
FAU - Powell, John
AU  - Powell J
FAU - Hodges, Angela
AU  - Hodges A
FAU - Nelson, Sally K
AU  - Nelson SK
FAU - Stewart, Alex
AU  - Stewart A
FAU - Williams, Stephen
AU  - Williams S
FAU - Kloszewska, Iwona
AU  - Kloszewska I
FAU - Mecocci, Patrizia
AU  - Mecocci P
FAU - Soininen, Hilkka
AU  - Soininen H
FAU - Tsolaki, Magda
AU  - Tsolaki M
FAU - Vellas, Bruno
AU  - Vellas B
FAU - Lovestone, Simon
AU  - Lovestone S
CN  - AddNeuroMed Consortium
FAU - Dobson, Richard
AU  - Dobson R
CN  - Alzheimer's Disease Neuroimaging Initiative
LA  - eng
GR  - K01 AG030514/AG/NIA NIH HHS/United States
GR  - P30 AG010129/AG/NIA NIH HHS/United States
GR  - U01 AG024904/AG/NIA NIH HHS/United States
GR  - U19 AG010483/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120516
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Aptamers, Nucleotide)
RN  - 0 (Blood Proteins)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Aptamers, Nucleotide
MH  - Blood Proteins/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Single Nucleotide
MH  - Proteomics/methods
MH  - Quantitative Trait Loci
MH  - *Regulatory Sequences, Nucleic Acid
PMC - PMC6446535
EDAT- 2012/05/19 06:00
MHDA- 2013/02/07 06:00
PMCR- 2013/08/15
CRDT- 2012/05/19 06:00
PHST- 2012/05/19 06:00 [entrez]
PHST- 2012/05/19 06:00 [pubmed]
PHST- 2013/02/07 06:00 [medline]
PHST- 2013/08/15 00:00 [pmc-release]
AID - dds186 [pii]
AID - 10.1093/hmg/dds186 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2012 Aug 15;21(16):3719-26. doi: 10.1093/hmg/dds186. Epub 2012 May 
      16.