Abstract:
:The current understanding of the genetic architecture of lipids has largely come from genome-wide association studies (GWAS). To date, few GWAS have examined the genetic architecture of lipids in Polynesians, and none have in Samoans, whose unique population history, including many population bottlenecks, may provide insight into the biological foundations of variation in lipid levels. Here we performed a GWAS of four fasting serum lipid levels: total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG) in a sample of 2849 Samoans, with validation genotyping for associations in a replication cohort comprising 1798 Samoans and American Samoans. We identified multiple genome-wide significant associations (P < 5 × 10-8) previously seen in other populations-APOA1 with TG, CETP with HDL, and APOE with TC and LDL-and several suggestive associations (P < 1 × 10-5), including an association of variants downstream of MGAT1 and RAB21 with HDL. However, we observed different association signals for variants near APOE than what has been previously reported in non-Polynesian populations. The association with several known lipid loci combined with the newly identified associations with variants near MGAT1 and RAB21 suggest that while some of the genetic architecture of lipids is shared between Samoans and other populations, part of the genetic architecture may be Polynesian-specific.
journal_name
J Hum Genetjournal_title
Journal of human geneticsauthors
Carlson JC,Weeks DE,Hawley NL,Sun G,Cheng H,Naseri T,Reupena MS,Tuitele J,Deka R,McGarvey ST,Minster RLdoi
10.1038/s10038-020-0816-9subject
Has Abstractpub_date
2021-02-01 00:00:00pages
111-121issue
2eissn
1434-5161issn
1435-232Xpii
10.1038/s10038-020-0816-9journal_volume
66pub_type
杂志文章abstract::In successive reports from 2014 to 2015, X-ray repair cross-complementing protein 4 (XRCC4) has been identified as a novel causative gene of primordial dwarfism. XRCC4 is indispensable for non-homologous end joining (NHEJ), the major pathway for repairing DNA double-strand breaks. As NHEJ is essential for V(D)J recomb...
journal_title:Journal of human genetics
pub_type: 杂志文章,评审
doi:10.1038/jhg.2016.46
更新日期:2016-08-01 00:00:00
abstract::Two novel mutations in the gene encoding T-protein, a component of the glycine cleavage system, were identified in a Japanese family with nonketotic hyperglycinemia. The proband had two affected sibs, and enzymatic analysis of the liver sample from the proband revealed the T-protein deficiency. The first mutation, 183...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050055
更新日期:1998-01-01 00:00:00
abstract::Chromosome 5, especially the 5q31-33 region, may contain one or more loci to control total serum IgE as well as asthma and bronchial hyperresponsiveness. To investigate the regions related with IgE level in chromosome 5, we performed a case-control association study on 105 high-IgE-level and 85 normal-IgE-level asthma...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-004-0215-7
更新日期:2005-01-01 00:00:00
abstract::MicroRNAs (miRNAs) are endogenous non-coding RNAs that function as negative regulators of gene expression. Alterations in miRNA expression have been shown to affect tumor growth and response to chemotherapy. In this study, we explored the possible role of miRNAs in cisplatin resistance in esophageal squamous cell carc...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2011.1
更新日期:2011-04-01 00:00:00
abstract::Genome-wide single nucleotide polymorphism (SNP) association studies recently identified four SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) on chromosome 9p21 that were associated with coronary artery disease (CAD) and myocardial infarction (MI) in Caucasian populations from northern Europe and North America...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0230-6
更新日期:2008-01-01 00:00:00
abstract::Site-1 protease (S1P) is a subtilisin-related enzyme that cleaves sterol regulatory element-binding proteins (SREBPs) in the lumen of endoplasmic reticulum, thereby initiating the release of transcriptionally active NH2-terminal fragments of SREBPs from membranes. In the experiments reported here, we localized the hum...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380070029
更新日期:2000-01-01 00:00:00
abstract::The scavenger receptor class B type 1 (SCARB1) gene is a key component in the reverse cholesterol transport pathway and thus plays an important role in lipid metabolism. Studies suggest that the SCARB1 gene may contribute to variation in plasma lipid levels at fasting; however, the results have been inconsistent, and ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-008-0302-2
更新日期:2008-01-01 00:00:00
abstract::Genetic testing for BRCA1/2 mutations has become the standard clinical practice. Recent findings suggest the clinical significance of multigene panel testing of BRCA1/2 and other cancer-related genes. However, the clinical features of patients with breast cancer with germline mutations identified using multigene panel...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-020-0729-7
更新日期:2020-07-01 00:00:00
abstract::Behçet disease (BD) is an immune-mediated disease. The cause of BD remains unknown, but the existence of multiple pathological pathways is suspected, including different genetic factors. Polymorphisms in ERAP1 gene have been associated with an increased risk of BD. However, while current BD-associated ERAP1 variants a...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-019-0709-y
更新日期:2020-03-01 00:00:00
abstract::The Japanese Genetic Research Group for Eating Disorders (JGRED) is a multisite collaborative study group that was organized for the systematic recruitment of patients with an eating disorder for the purpose of genetic study in Japan. We conducted a genome-wide case-control association study using 23 465 highly polymo...
journal_title:Journal of human genetics
pub_type: 杂志文章,多中心研究
doi:10.1038/jhg.2009.74
更新日期:2009-09-01 00:00:00
abstract::The alpha 2-adrenergic receptors (alpha2-AR) mediate physiological effects of epinephrine and norepinephrine. Three genes encode alpha2-AR subtypes carrying common functional polymorphisms (ADRA2A Asn251Lys, ADRA2B Ins/Del301-303 and ADRA2C Ins/Del322-325). We genotyped these functional markers plus a panel of single ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-004-0211-y
更新日期:2005-01-01 00:00:00
abstract::It is well known that individuals with low, or lack of, antibody production in response to hepatitis B surface antigen (HBsAg) exist in the human population. We have previously reported that HLA class I and class II genes are both involved in antibody production to HBsAg, and that specific alleles of HLA are associate...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380170089
更新日期:2001-01-01 00:00:00
abstract::CYP2C9 is the key enzyme in aromatic antiepileptic drugs (AEDs) metabolism. CYP2C9*3 is a loss of function polymorphism. This study was designed to investigate genetic association between CYP2C9*3 and aromatic AED-induced severe cutaneous adverse reactions (SCARs) in Thai children. The 37 aromatic AED-induced SCARs pa...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2015.47
更新日期:2015-08-01 00:00:00
abstract::Glutathione synthetase deficiency is a rare autosomal recessive disorder resulting in low levels of glutathione and an increased susceptibility to oxidative stress. Patients with glutathione synthetase deficiency typically present in the neonatal period with hemolytic anemia, metabolic acidosis and neurological impair...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2016.20
更新日期:2016-07-01 00:00:00
abstract::Using genome-editing technologies to correct specific mutations represents a potentially transformative new approach for treating genetic disorders. Despite rapid advances in the field of genome editing, it is still unclear whether the long-standing goal of in vivo targeted transgene integration is feasible. This is p...
journal_title:Journal of human genetics
pub_type: 杂志文章,评审
doi:10.1038/s10038-017-0352-4
更新日期:2018-02-01 00:00:00
abstract::Approximately one-third of the mammalian genome is composed of highly repeated DNA sequences, of which the two major families, the long and short inter-spersed nucleotide elements (LINEs and SINEs), are represented in humans by L1 and Alu elements respectively. Both 'types of element are considered to be retrotranspos...
journal_title:Journal of human genetics
pub_type: 杂志文章,评审
doi:10.1007/s100380050045
更新日期:1998-01-01 00:00:00
abstract::The KCNQ2 gene codifies a subunit of the voltage-gated potassium M channel underlying the neuronal M-current. Classically, mutations in this gene have been associated with benign familial neonatal seizures, however, in recent years KCNQ2 mutations have been reported associated to early-onset epileptic encephalopathy. ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2016.104
更新日期:2017-02-01 00:00:00
abstract::The name Fon-Jou Hsieh was inadvertently omitted from the list of authors. The name should be added as the third author of the article. ...
journal_title:Journal of human genetics
pub_type: 杂志文章,已发布勘误
doi:10.1007/s10038-006-0367-8
更新日期:2006-03-01 00:00:00
abstract::Fucosidosis is a rare lysosomal storage disease caused by a defect of the alpha-L: -fucosidase (FUCA1) gene. Worldwide 26 mutations underlying the disease have been reported. By direct DNA sequencing of exons and flanking introns, homozygous Y126X mutation and Q281R polymorphism were found in a Taiwanese patient with ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0136-3
更新日期:2007-01-01 00:00:00
abstract::GATA zinc finger domain-containing 2B (GATAD2B) is a subunit of the methyl-CpG-binding protein-1 complex (MECP1), which deacetylates methylated nucleosomes and regresses transcriptional activity. Recently, GATAD2B has been elucidated as a candidate gene in patients with intellectual disability (ID). In this study, we ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2016.164
更新日期:2017-04-01 00:00:00
abstract::Multiple pterygium syndrome (MPS) is an autosomal recessively inherited condition that becomes evident before birth, with pterygium at multiple joints and akinesia. There are two forms of this syndrome that are differentiated by clinical severity: the milder form, Escobar type (OMIM#265000), and the more severe form, ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2015.2
更新日期:2015-04-01 00:00:00
abstract::Prader-Willi syndrome (PWS) is primarily caused by deletions involving the paternally derived imprinted region at chromosome 15q11.2-q13 and maternal uniparental disomy 15 (upd(15)mat). The underlying mechanisms for upd(15)mat include trisomy rescue (TR), gamete complementation (GC), monosomy rescue and post-fertiliza...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2011.59
更新日期:2011-08-01 00:00:00
abstract::Adrenomedullin (ADM), a peptide characterized by persistent hypotensive activity, is thought to be involved when the control mechanism of blood pressure is deranged, because its plasma concentration is upregulated in hypertensive patients. The receptor for ADM, a molecular complex consisting of calcitonin-receptor-lik...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380170100
更新日期:2001-01-01 00:00:00
abstract::The expansion of polyalanine repeats is known to cause at least nine disorders, including congenital central hypoventilation syndrome (CCHS). Unequal crossover has been speculated as the expanding mechanism, in contrast to strand slippage in polyglutamine expansion disorders. We carried out segregation analysis of PHO...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0197-3
更新日期:2007-01-01 00:00:00
abstract::The widely used Western BRCA mutation prediction models underestimated the risk of having a BRCA mutation in Korean breast cancer patients. This study aimed to identify predictive factors for BRCA1/2 mutations and to develop a Korean BRCA risk calculator. The model was constructed by logistic regression model, and it ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2015.164
更新日期:2016-05-01 00:00:00
abstract::Carnitine-acylcarnitine translocase (CACT) and carnitine palmitoyltransferase II (CPT2) are key enzymes for transporting long-chain fatty acids into mitochondria. Deficiencies of these enzymes, which are clinically characterized by life-threatening non-ketotic hypoglycemia and rhabdomyolysis, cannot be distinguished b...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2013.103
更新日期:2013-12-01 00:00:00
abstract::The House of Aisin Gioro is the imperial family of the last dynasty in Chinese history-Qing dynasty (1644-1911). The Aisin Gioro family originated from Jurchen tribes and founded the Manchu people before they conquered China. By investigating the Y chromosomal short tandem repeats (STRs) of seven modern male individua...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2015.28
更新日期:2015-06-01 00:00:00
abstract::PLA2G6-associated neurodegeneration (PLAN) comprises heterogeneous neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation 2B, and Parkinson disease 14 (PARK14). In addition, very recently, PLA2G6 mutations have been reported to represent a phenotype of he...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-018-0519-7
更新日期:2019-01-01 00:00:00
abstract::BBS8 is one of the eight genes identified to date for Bardet-Biedl syndrome (BBS)-an autosomal recessive condition associated with retinitis pigmentosa, obesity, polydactyly, cognitive impairment and kidney failure. The identification of BBS8 gave the key to the pathogenesis of the condition as a primary ciliary disor...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-005-0320-2
更新日期:2006-01-01 00:00:00
abstract::Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase (CYP21) gene. More than 90% of CAH cases are caused by mutations of the CYP21 gene. Approximately 75% of the defective CYP21 genes are generated through intergenic recombination, termed ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380200077
更新日期:2002-01-01 00:00:00