TY - JOUR
T1 - Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
AU - BBMRI Metabolomics Consortium
AU - Hagenbeek, Fiona A.
AU - Bomer, N.
AU - van Hilten, J. A.
AU - Fu, J.
AU - van der Heijden, A. A.W.A.
AU - van der Spek, A.
AU - Boersma, E.
AU - van den Akker, E. B.
AU - Reinders, M. J.T.
AU - More Authors, null
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2 Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2 Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.
AB - Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2 Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2 Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.
UR - http://www.scopus.com/inward/record.url?scp=85077630105&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-13770-6
DO - 10.1038/s41467-019-13770-6
M3 - Article
C2 - 31911595
AN - SCOPUS:85077630105
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 39
ER -