TY - JOUR
T1 - Genetics and Not Shared Environment Explains Familial Resemblance in Adult Metabolomics Data
AU - Pool, R
AU - Hagenbeek, FA
AU - Hendriks, AM
AU - van Dongen, J
AU - Willemsen, G
AU - de Geus, E
AU - van Dijk, KW
AU - Verhoeven, A
AU - Suchiman, HE
AU - Beekman, M
AU - Slagboom, PE
AU - Harms, AC
AU - Hankemeier, T
AU - Boomsma, D
AU - Beekman, M
AU - Suchiman, HED
AU - Amin, N
AU - Beulens, JW
AU - van der Bom, JA
AU - Bomer, N
AU - Demirkan, A
AU - van Hilten, JA
AU - Meessen, JMTA
AU - Pool, R
AU - Moed, MH
AU - Fu, J
AU - Onderwater, GLJ
AU - Rutters, F
AU - So-Osman, C
AU - van der Flier, WM
AU - van der Heijden, AAWA
AU - van der Spek, A
AU - Asselbergs, FW
AU - Boersma, E
AU - Elders, PM
AU - Geleijnse, JM
AU - Ikram, MA
AU - Kloppenburg, M
AU - Meulenbelt, I
AU - Mooijaart, SP
AU - Nelissen, RGHH
AU - Netea, MG
AU - Penninx, BWJH
AU - Stehouwer, CDA
AU - Teunissen, CE
AU - Terwindt, GM
AU - 't Hart, LM
AU - van den Maagdenberg, AMJM
AU - van der Harst, P
AU - van der Horst, ICC
AU - van der Kallen, CJH
AU - van Greevenbroek, MMJ
AU - van Spil, WE
AU - Wijmenga, C
AU - Zwinderman, AH
AU - Zhernikova, A
AU - Jukema, JW
AU - Wolf, JJHB
AU - Cats, D
AU - Mei, H
AU - Slofstra, M
AU - Swertz, M
AU - van den Akker, EB
AU - Deelen, J
AU - Reinders, MJT
AU - Boomsma, D
AU - van Duijn, CM
AU - Slagboom, PE
AU - BBMRI-NL Metabolomics Consortium
AU - Hendriks, Anne M.
AU - van Dijk, Ko Willems
AU - Consortium, Consortium M.
PY - 2020/7/8
Y1 - 2020/7/8
N2 - Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term 'metabolomics' refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.
AB - Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term 'metabolomics' refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.
KW - Classical twin design
KW - Keywords: Classical twin design
KW - enrichment analysis
KW - heritability
KW - metabolite classes
KW - shared environment
UR - http://www.scopus.com/inward/record.url?scp=85087669773&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85087669773&partnerID=8YFLogxK
U2 - https://doi.org/10.1017/thg.2020.53
DO - https://doi.org/10.1017/thg.2020.53
M3 - Article
C2 - 32635965
SN - 1832-4274
VL - 23
SP - 145
EP - 155
JO - Twin research and human genetics
JF - Twin research and human genetics
IS - 3
ER -