Identification of seven novel loci associated with amino acid levels using single-variant and gene-based tests in 8545 Finnish men from the METSIM study. ...

• Main Authors: Teslovich, Tanya M, Kim, Daniel Seung, Yin, Xianyong, Stancáková, Alena, Jackson, Anne U, Wielscher, Matthias, Naj, Adam, Perry, John RB, Huyghe, Jeroen R, Stringham, Heather M, Davis, James P, Raulerson, Chelsea K, Welch, Ryan P, Fuchsberger, Christian, Locke, Adam E, Sim, Xueling, Chines, Peter S, Narisu, Narisu, Kangas, Antti J, Soininen, Pasi, Genetics Of Obesity-Related Liver Disease Consortium GOLD, The Alzheimer's Disease Genetics Consortium ADGC, The DIAbetes Genetics Replication And Meta-Analysis DIAGRAM, Ala-Korpela, Mika, Gudnason, Vilmundur, Musani, Solomon K, Jarvelin, Marjo-Riitta, Schellenberg, Gerard D, Speliotes, Elizabeth K, Kuusisto, Johanna, Collins, Francis S, Boehnke, Michael, Laakso, Markku, Mohlke, Karen L
• Format: Article in Journal/Newspaper
• Language: English
• Published: OUP 2018
• Subjects: Amino Acids; Finland; Gene Frequency; Genome-Wide Association Study; Genotype; Humans; Male; Middle Aged; Northern Finland
• Online Access: https://dx.doi.org/10.17863/cam.30345; https://www.repository.cam.ac.uk/handle/1810/282983

Comprehensive metabolite profiling captures many highly heritable traits, including amino acid levels, which are potentially sensitive biomarkers for disease pathogenesis. To better understand the contribution of genetic variation to amino acid levels, we performed single variant and gene-based tests of association between nine serum amino acids (alanine, glutamine, glycine, histidine, isoleucine, leucine, phenylalanine, tyrosine, and valine) and 16.6 million genotyped and imputed variants in 8545 non-diabetic Finnish men from the METabolic Syndrome In Men (METSIM) study with replication in Northern Finland Birth Cohort (NFBC1966). We identified five novel loci associated with amino acid levels (P = < 5×10-8): LOC157273/PPP1R3B with glycine (rs9987289, P = 2.3×10-26); ZFHX3 (chr16:73326579, minor allele frequency (MAF) = 0.42%, P = 3.6×10-9), LIPC (rs10468017, P = 1.5×10-8), and WWOX (rs9937914, P = 3.8×10-8) with alanine; and TRIB1 with tyrosine (rs28601761, P = 8×10-9). Gene-based tests identified two ...