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

Human Molecular Genetics
Tanya M TeslovichKaren L Mohlke

Abstract

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 novel genes harboring missense variants of MAF <1% that show aggregate association with amino acid levels: PYCR1 with glycine (Pgene = 1.5×10-6) and BCAT2 with valine (Pgene = 7.4×10-7); neither gene was implicated by single var...Continue Reading

References

Jan 1, 1988·Paediatric and Perinatal Epidemiology·P Rantakallio
Oct 9, 1969·The New England Journal of Medicine·P FeligG F Cahill
Apr 1, 1981·The Journal of Clinical Investigation·G C YehJ M Phang
Sep 29, 2006·Molecular Genetics and Metabolism·Kim L McBrideBrendan H Lee
Oct 30, 2007·American Journal of Human Genetics·Karen N Conneely, Michael Boehnke
May 20, 2008·The Journal of Biological Chemistry·Rami I AqeilanCarlo M Croce
Dec 9, 2008·Nature Genetics·Sekar KathiresanL Adrienne Cupples
Jul 7, 2009·American Journal of Human Genetics·Duane L GuernseyMark E Samuels
Aug 4, 2009·Nature Genetics·Bruno ReversadeUwe Kornak
Jun 22, 2010·Nature Genetics·Jian YangPeter M Visscher
Aug 6, 2010·Nature·Tanya M TeslovichSekar Kathiresan
Oct 12, 2010·Bioinformatics·Ani ManichaikulWei-Min Chen
Sep 3, 2011·Nature·Karsten SuhreChristian Gieger
Dec 14, 2011·Human Molecular Genetics·Taru TukiainenSamuli Ripatti
Dec 22, 2011·Circulation. Cardiovascular Genetics·Siddharth Prakash
Apr 19, 2012·Diabetes·Peter WürtzMika Ala-Korpela
Dec 28, 2012·Nature Methods·Olivier DelaneauJonathan Marchini
Jul 5, 2013·Cell Metabolism·Eugene P RheeRobert E Gerszten
Oct 8, 2013·Nature Genetics·Cristen J WillerUNKNOWN Global Lipids Genetics Consortium
Nov 28, 2013·World Journal of Gastroenterology : WJG·Kazuto Tajiri, Yukihiro Shimizu
Feb 11, 2014·American Journal of Human Genetics·Leslie A LangeUNKNOWN NHLBI Grand Opportunity Exome Sequencing Project
May 13, 2014·Nature Genetics·So-Youn ShinNicole Soranzo
May 30, 2014·Circulation. Cardiovascular Genetics·Iulia IatanJacques Genest
Jul 6, 2014·American Journal of Human Genetics·Seunggeung LeeXihong Lin
Oct 22, 2014·Open Heart·Mark F McCarty, James J DiNicolantonio
Oct 24, 2014·Bioinformatics·Christian FuchsbergerDavid A Hinds
Feb 19, 2015·Circulation. Cardiovascular Genetics·Pasi SoininenMika Ala-Korpela
Apr 17, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Matthew J KanCarol A Colton
Oct 4, 2015·Nature·Peter H SudmantJan O Korbel
Jul 12, 2016·Nature·Christian FuchsbergerMark I McCarthy
Jul 28, 2016·Nature Communications·Eugene P RheeRobert E Gerszten
Aug 23, 2016·Nature Genetics·Shane McCarthyUNKNOWN Haplotype Reference Consortium

❮ Previous
Next ❯

Citations

May 10, 2019·Journal of the American Heart Association·Qiong JiaHooman Allayee
Oct 5, 2019·European Journal of Human Genetics : EJHG·Debashree Ray, Nilanjan Chatterjee
Oct 12, 2019·Journal of Inherited Metabolic Disease·Lynne RumpingNanda M Verhoeven-Duif
Mar 7, 2019·Nature Communications·Laura B L WittemansClaudia Langenberg
Mar 10, 2020·PLoS Genetics·Fernando Riveros-MckayInês Barroso
Oct 10, 2018·Genetic Epidemiology·Diptavo DuttaSeunggeun Lee
Feb 16, 2021·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·Rocío Guizar-HerediaMartha Guevara-Cruz

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.