ArticleAmerican journal of human genetics2013
Joint linkage and association analysis with exome sequence data implicates SLC25A40 in hypertriglyceridemia.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- The impact of solute carrier proteins on disrupting substance regulation in metabolic disorders: insights and clinical applications.Frontiers in pharmacology · 2024Review
- Genetic Origins of the Two Canis lupus familiaris (Dog) Freight Dog Populations.The Journal of heredity · 2022Article
- Whole-genome sequencing identifies functional noncoding variation in SEMA3C that cosegregates with dyslexia in a multigenerational family.Human genetics · 2021Article
- Association between triglycerides, known risk SNVs and conserved rare variation in SLC25A40 in a multi-ancestry cohort.BMC medical genomics · 2021Article
- Review
- Arctic-adapted dogs emerged at the Pleistocene-Holocene transition.Science (New York, N.Y.) · 2020Article
- 20,000 picometers under the OMM: diving into the vastness of mitochondrial metabolite transport.EMBO reports · 2020Review
- Diseases Caused by Mutations in Mitochondrial Carrier GenesBiomolecules · 2020Review
- Emerging Roles in the Biogenesis of CytochromeFrontiers in cell and developmental biology · 2019Review
- Identity-by-Descent Mapping Identifies Major Locus for Serum Triglycerides in Amerindians Largely Explained by anCirculation. Cardiovascular genetics · 2017Article
- Power of pedigree likelihood analysis in extended pedigrees to classify rare variants of uncertain significance in cancer risk genes.Familial cancer · 2017Article
- Analysis with the exome array identifies multiple new independent variants in lipid loci.Human molecular genetics · 2016Article
- Shawn, the Drosophila Homolog of SLC25A39/40, Is a Mitochondrial Carrier That Promotes Neuronal Survival.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Insights into blood lipids from rare variant discovery.Current opinion in genetics & development · 2015Review
- Insights from exome sequencing for endocrine disorders.Nature reviews. Endocrinology · 2015Review
- Leveraging Identity-by-Descent for Accurate Genotype Inference in Family Sequencing Data.PLoS genetics · 2015Article
- Next-generation gene discovery for variants of large impact on lipid traits.Current opinion in lipidology · 2015Review
- Genetic and environmental determinants of the susceptibility of Amerindian derived populations for having hypertriglyceridemia.Metabolism: clinical and experimental · 2014Review
- A statistical framework to guide sequencing choices in pedigrees.American journal of human genetics · 2014Article
- Review of current methods, applications, and data management for the bioinformatics analysis of whole exome sequencing.Cancer informatics · 2014Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Hypertriglyceridemia (HTG) is a heritable risk factor for cardiovascular disease. Investigating the genetics of HTG may identify new drug targets. There are ~35 known single-nucleotide variants (SNVs) that explain only ~10% of variation in triglyceride (TG) level. Because of the genetic heterogeneity of HTG, a family study design is optimal for identification of rare genetic variants with large effect size because the same mutation can be observed in many relatives and cosegregation with TG can be tested. We considered HTG in a five-generation family of European American descent (n = 121), ascertained for familial combined hyperlipidemia. By using Bayesian Markov chain Monte Carlo joint oligogenic linkage and association analysis, we detected linkage to chromosomes 7 and 17. Whole-exome sequence data revealed shared, highly conserved, private missense SNVs in both SLC25A40 on chr7 and PLD2 on chr17. Jointly, these SNVs explained 49% of the genetic variance in TG; however, only the SLC25A40 SNV was significantly associated with TG (p = 0.0001). This SNV, c.374A>G, causes a highly disruptive p.Tyr125Cys substitution just outside the second helical transmembrane region of the SLC25A40 inner mitochondrial membrane transport protein. Whole-gene testing in subjects from the Exome Sequencing Project confirmed the association between TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03). These results suggest a previously undescribed pathway for HTG and illustrate the power of large pedigrees in the search for rare, causal variants.
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