Details

Autor(en) / Beteiligte

• Fu, Jingyuan
• Wolfs, Marcel G M
• Deelen, Patrick
• Westra, Harm-Jan
• Fehrmann, Rudolf S N
• Te Meerman, Gerard J
• Buurman, Wim A
• Rensen, Sander S M
• Groen, Harry J M
• Weersma, Rinse K
• van den Berg, Leonard H
• Veldink, Jan
• Ophoff, Roel A
• Snieder, Harold
• van Heel, David
• Jansen, Ritsert C
• Hofker, Marten H
• Wijmenga, Cisca
• Franke, Lude
• Gibson, Greg

Titel

Unraveling the regulatory mechanisms underlying tissue-dependent genetic variation of gene expression

Ist Teil von

• PLoS genetics, 2012-01, Vol.8 (1), p.e1002431

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• It is known that genetic variants can affect gene expression, but it is not yet completely clear through what mechanisms genetic variation mediate this expression. We therefore compared the cis-effect of single nucleotide polymorphisms (SNPs) on gene expression between blood samples from 1,240 human subjects and four primary non-blood tissues (liver, subcutaneous, and visceral adipose tissue and skeletal muscle) from 85 subjects. We characterized four different mechanisms for 2,072 probes that show tissue-dependent genetic regulation between blood and non-blood tissues: on average 33.2% only showed cis-regulation in non-blood tissues; 14.5% of the eQTL probes were regulated by different, independent SNPs depending on the tissue of investigation. 47.9% showed a different effect size although they were regulated by the same SNPs. Surprisingly, we observed that 4.4% were regulated by the same SNP but with opposite allelic direction. We show here that SNPs that are located in transcriptional regulatory elements are enriched for tissue-dependent regulation, including SNPs at 3' and 5' untranslated regions (P = 1.84×10(-5) and 4.7×10(-4), respectively) and SNPs that are synonymous-coding (P = 9.9×10(-4)). SNPs that are associated with complex traits more often exert a tissue-dependent effect on gene expression (P = 2.6×10(-10)). Our study yields new insights into the genetic basis of tissue-dependent expression and suggests that complex trait associated genetic variants have even more complex regulatory effects than previously anticipated.