2020
DOI: 10.1016/j.ajhg.2020.09.003
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A Genome-wide Association Study Discovers 46 Loci of the Human Metabolome in the Hispanic Community Health Study/Study of Latinos

Abstract: Variation in levels of the human metabolome reflect changes in homeostasis, providing a window into health and disease. The genetic impact on circulating metabolites in Hispanics, a population with high cardiometabolic disease burden, is largely unknown. We conducted genome-wide association analyses on 640 circulating metabolites in 3,926 Hispanic Community Health Study/Study of Latinos participants. The estimated heritability for 640 metabolites ranged between 0%-54% with a median at 2.5%. We discovered 46 va… Show more

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Cited by 63 publications
(77 citation statements)
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“…However, we did confirm greater estrone sulfate concentrations in individuals with the SLCO1B1 c.521T>C allele as was previously reported ( van der Deure et al, 2008 ). But the multivariate model for plasma estrone sulfate concentrations was not particularly effective in explaining interindividual variability (R 2 = 0.047) indicating other genetic and biological factors are important ( Platia et al, 1984 ; Feofanova et al, 2020 ).…”
Section: Discussionmentioning
confidence: 94%
“…However, we did confirm greater estrone sulfate concentrations in individuals with the SLCO1B1 c.521T>C allele as was previously reported ( van der Deure et al, 2008 ). But the multivariate model for plasma estrone sulfate concentrations was not particularly effective in explaining interindividual variability (R 2 = 0.047) indicating other genetic and biological factors are important ( Platia et al, 1984 ; Feofanova et al, 2020 ).…”
Section: Discussionmentioning
confidence: 94%
“…79 Metabolon continues to expand the set of metabolites identified on their platform. 78 of the 303 novel association signals were for 44 metabolites identified after 2015 on the Metabolon DiscoveryHD4 platform, and so studied only in the most recent Metabolon-based metabolomics GWAS 13 . For example, we identified a novel association at SLC23A3 missense variant p.Asn336Lys for 2-O-methylascorbic acid, identified on the Metabolon platform in 2019.…”
Section: Discussionmentioning
confidence: 99%
“…Many metabolites are highly heritable, and previous metabolite GWAS have identified common variants [5][6][7][8][9][10][11][12][13][14][15] ; the impact of rare variants on metabolites is less well studied 16,17 .…”
Section: Main Text (3890 Words)mentioning
confidence: 99%
“…Feofanova et al [100] conducted GWAS on 640 circulating metabolites in 3926 Hispanic Community Health Study/Study of Latinos participants and replicated the results in 1509 participants in the ARIC study. In their MR study, the novel findings were that 1 SD increase in 1-arachidonylglycerol (20:4) (OR 1.13, 95% CI, 1.06-1.21) and 1-palmitoyl-2-stearoyl-GPC (16:0/18:0) (OR 1.24, 95% CI, 1.10-1.40) increased the risk of T2D and that 1 SD increase in gamma-CEHC (OR 0.84, 95% CI 0.78-0.91), gamma-CEHC glucuronide (OR 0.77, 95% CI, 0.67-0.87), and octadecanedioate (OR 0.81, 95% CI, 0.81-0.90) decreased the risk of CAD.…”
Section: Mendelian Randomization Studies On Metabolites In Type 2 Diabetes and Cardiovascular Diseasementioning
confidence: 94%