Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
Am J Hum Genet ; 105(1): 65-77, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31204010

RESUMO

The Genes for Good study uses social media to engage a large, diverse participant pool in genetics research and education. Health history and daily tracking surveys are administered through a Facebook application, and participants who complete a minimum number of surveys are mailed a saliva sample kit ("spit kit") to collect DNA for genotyping. As of March 2019, we engaged >80,000 individuals, sent spit kits to >32,000 individuals who met minimum participation requirements, and collected >27,000 spit kits. Participants come from all 50 states and include a diversity of ancestral backgrounds. Rates of important chronic health indicators are consistent with those estimated for the general U.S. population using more traditional study designs. However, our sample is younger and contains a greater percentage of females than the general population. As one means of verifying data quality, we have replicated genome-wide association studies (GWASs) for exemplar traits, such as asthma, diabetes, body mass index (BMI), and pigmentation. The flexible framework of the web application makes it relatively simple to add new questionnaires and for other researchers to collaborate. We anticipate that the study sample will continue to grow and that future analyses may further capitalize on the strengths of the longitudinal data in combination with genetic information.

3.
Circ Genom Precis Med ; 12(6): e002476, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31211624

RESUMO

BACKGROUND: Thoracic aortic dissection is an emergent life-threatening condition. Routine screening for genetic variants causing thoracic aortic dissection is not currently performed for patients or family members. METHODS: We performed whole exome sequencing of 240 patients with thoracic aortic dissection (n=235) or rupture (n=5) and 258 controls matched for age, sex, and ancestry. Blinded to case-control status, we annotated variants in 11 genes for pathogenicity. RESULTS: Twenty-four pathogenic variants in 6 genes (COL3A1, FBN1, LOX, PRKG1, SMAD3, and TGFBR2) were identified in 26 individuals, representing 10.8% of aortic cases and 0% of controls. Among dissection cases, we compared those with pathogenic variants to those without and found that pathogenic variant carriers had significantly earlier onset of dissection (41 versus 57 years), higher rates of root aneurysm (54% versus 30%), less hypertension (15% versus 57%), lower rates of smoking (19% versus 45%), and greater incidence of aortic disease in family members. Multivariable logistic regression showed that pathogenic variant carrier status was significantly associated with age <50 (odds ratio [OR], 5.5; 95% CI, 1.6-19.7), no history of hypertension (OR, 5.6; 95% CI, 1.4-22.3), and family history of aortic disease (mother: OR, 5.7; 95% CI, 1.4-22.3, siblings: OR, 5.1; 95% CI, 1.1-23.9, children: OR, 6.0; 95% CI, 1.4-26.7). CONCLUSIONS: Clinical genetic testing of known hereditary thoracic aortic dissection genes should be considered in patients with a thoracic aortic dissection, followed by cascade screening of family members, especially in patients with age-of-onset <50 years, family history of thoracic aortic disease, and no history of hypertension.

4.
Nat Neurosci ; 22(3): 503, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30622366

RESUMO

The author list was in the wrong order in the HTML version of the original article and in the HTML version of the original correction notice. This has been corrected to show the 23andMe Research Team as the fourth author and Abraham A. Palmer as the last author in both places.

5.
Nat Genet ; 50(11): 1505-1513, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30297969

RESUMO

We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%, 14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).

6.
Nat Genet ; 50(9): 1234-1239, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30061737

RESUMO

To identify genetic variation underlying atrial fibrillation, the most common cardiac arrhythmia, we performed a genome-wide association study of >1,000,000 people, including 60,620 atrial fibrillation cases and 970,216 controls. We identified 142 independent risk variants at 111 loci and prioritized 151 functional candidate genes likely to be involved in atrial fibrillation. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans (GATA4, MYH6, NKX2-5, PITX2, TBX5)1, or near genes important for striated muscle function and integrity (for example, CFL2, MYH7, PKP2, RBM20, SGCG, SSPN). Pathway and functional enrichment analyses also suggested that many of the putative atrial fibrillation genes act via cardiac structural remodeling, potentially in the form of an 'atrial cardiomyopathy'2, either during fetal heart development or as a response to stress in the adult heart.

7.
Am J Hum Genet ; 102(6): 1048-1061, 2018 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-29779563

RESUMO

Health systems are stewards of patient electronic health record (EHR) data with extraordinarily rich depth and breadth, reflecting thousands of diagnoses and exposures. Measures of genomic variation integrated with EHRs offer a potential strategy to accurately stratify patients for risk profiling and discover new relationships between diagnoses and genomes. The objective of this study was to evaluate whether polygenic risk scores (PRS) for common cancers are associated with multiple phenotypes in a phenome-wide association study (PheWAS) conducted in 28,260 unrelated, genotyped patients of recent European ancestry who consented to participate in the Michigan Genomics Initiative, a longitudinal biorepository effort within Michigan Medicine. PRS for 12 cancer traits were calculated using summary statistics from the NHGRI-EBI catalog. A total of 1,711 synthetic case-control studies was used for PheWAS analyses. There were 13,490 (47.7%) patients with at least one cancer diagnosis in this study sample. PRS exhibited strong association for several cancer traits they were designed for, including female breast cancer, prostate cancer, melanoma, basal cell carcinoma, squamous cell carcinoma, and thyroid cancer. Phenome-wide significant associations were observed between PRS and many non-cancer diagnoses. To differentiate PRS associations driven by the primary trait from associations arising through shared genetic risk profiles, the idea of "exclusion PRS PheWAS" was introduced. Further analysis of temporal order of the diagnoses improved our understanding of these secondary associations. This comprehensive PheWAS used PRS instead of a single variant.

8.
Nat Neurosci ; 21(7): 1018, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29752479

RESUMO

In the version of this article initially published, the consortium authorship was not presented correctly. The 23andMe Research Team was listed as the last author, rather than the fourth, and a line directing readers to the Supplementary Note for a list of members did appear but was not directly associated with the consortium name. Also, the Supplementary Note description stated that both member names and affiliations were included; in fact, only names are given. Finally, the URL for S-PrediXcan was given in the Methods as https://github.com/hakyimlab/S-PrediXcan; the correct URL is https://github.com/hakyimlab/MetaXcan. The errors have been corrected in the HTML and PDF versions of the article.

9.
Am J Hum Genet ; 102(1): 103-115, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29290336

RESUMO

Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 × 10-18) comprised intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle. The other novel locus (lead SNV rs56202902; p = 1.54 × 10-11) covered a large, gene-dense chromosome 1 region that has previously been linked to cardiac conduction. Pathway and functional enrichment analyses suggested that many AF-associated genetic variants act through a mechanism of impaired muscle cell differentiation and tissue formation during fetal heart development.

10.
Nat Neurosci ; 21(1): 16-18, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29230059

RESUMO

Delay discounting (DD), the tendency to discount the value of delayed versus current rewards, is elevated in a constellation of diseases and behavioral conditions. We performed a genome-wide association study of DD using 23,127 research participants of European ancestry. The most significantly associated single-nucleotide polymorphism was rs6528024 (P = 2.40 × 10-8), which is located in an intron of the gene GPM6B. We also showed that 12% of the variance in DD was accounted for by genotype and that the genetic signature of DD overlapped with attention-deficit/hyperactivity disorder, schizophrenia, major depression, smoking, personality, cognition and body weight.

11.
J Crit Care ; 44: 203-211, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29161666

RESUMO

PURPOSE: Limited data exists on potential genetic contributors to acute kidney injury. This review examines current knowledge of AKI genomics. MATERIALS AND METHODS: 32 studies were selected from PubMed and GWAS Catalog queries for original data studies of human AKI genetics. Hand search of references identified 3 additional manuscripts. RESULTS: 33 of 35 studies were hypothesis-driven investigations of candidate polymorphisms that either did not consistently replicate statistically significant findings, or obtained significant results only in few small-scale studies. Vote-counting meta-analysis of 9 variants examined in >1 candidate gene study showed ≥50% non-significant studies, with larger studies generally finding non-significant results. The remaining 2 studies were large-scale unbiased investigations: One examining 2,100 genes linked with cardiovascular, metabolic, and inflammatory syndromes identified BCL2, SERPINA4, and SIK3 variants, while a genome-wide association study (GWAS) identified variants in BBS9 and the GRM7|LMCD1-AS1 intergenic region. All studies had relatively small sample sizes (<2300 subjects). Study heterogeneity precluded candidate gene and GWA meta-analysis. CONCLUSIONS: Most studies of AKI genetics involve hypothesis-driven (rather than hypothesis-generating) candidate gene investigations that have failed to identify contributory variants consistently. A limited number of unbiased, larger-scale studies have been carried out, but there remains a pressing need for additional GWA studies.

12.
Am J Hum Genet ; 101(1): 37-49, 2017 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-28602423

RESUMO

The availability of electronic health record (EHR)-based phenotypes allows for genome-wide association analyses in thousands of traits and has great potential to enable identification of genetic variants associated with clinical phenotypes. We can interpret the phenome-wide association study (PheWAS) result for a single genetic variant by observing its association across a landscape of phenotypes. Because a PheWAS can test thousands of binary phenotypes, and most of them have unbalanced or often extremely unbalanced case-control ratios (1:10 or 1:600, respectively), existing methods cannot provide an accurate and scalable way to test for associations. Here, we propose a computationally fast score-test-based method that estimates the distribution of the test statistic by using the saddlepoint approximation. Our method is much (∼100 times) faster than the state-of-the-art Firth's test. It can also adjust for covariates and control type I error rates even when the case-control ratio is extremely unbalanced. Through application to PheWAS data from the Michigan Genomics Initiative, we show that the proposed method can control type I error rates while replicating previously known association signals even for traits with a very small number of cases and a large number of controls.


Assuntos
Algoritmos , Estudo de Associação Genômica Ampla , Simulação por Computador , Frequência do Gene/genética , Genômica , Humanos , Análise Numérica Assistida por Computador , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Fatores de Tempo
13.
Nat Genet ; 48(10): 1171-1184, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27618452

RESUMO

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.


Assuntos
Pressão Sanguínea/genética , Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Asiático/genética , Células Cultivadas , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/genética , Hipertensão/patologia , Análise em Microsséries , Polimorfismo de Nucleotídeo Único
14.
Nat Commun ; 7: 10495, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26833246

RESUMO

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.


Assuntos
Adiposidade/genética , Predisposição Genética para Doença , Cardiopatias/genética , Locos de Características Quantitativas/genética , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes , Estudo de Associação Genômica Ampla , Humanos
15.
Curr Opin Genet Dev ; 33: 25-31, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26241468

RESUMO

Large-scale genome wide screens have discovered over 160 common variants associated with plasma lipids, which are risk factors often linked to heart disease. A large fraction of lipid heritability remains unexplained, and it is hypothesized that rare variants of functional consequence may account for some of the missing heritability. Finding lipid-associated variants that occur less frequently in the human population poses a challenge, primarily due to lack of power and difficulties to identify and test them. Interrogation of the protein-coding regions of the genome using array and sequencing techniques has led to important discoveries of rare variants that affect lipid levels and related disease risk. Here, we summarize the latest methods and findings that contribute to our current understanding of rare variant lipid genetics.


Assuntos
Predisposição Genética para Doença , Variação Genética , Cardiopatias/genética , Lipídeos/genética , Frequência do Gene , Estudo de Associação Genômica Ampla , Cardiopatias/sangue , Cardiopatias/patologia , Humanos , Lipídeos/sangue , Fases de Leitura Aberta/genética , Polimorfismo de Nucleotídeo Único
16.
Bioinformatics ; 31(16): 2601-6, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25886982

RESUMO

MOTIVATION: The majority of variation identified by genome wide association studies falls in non-coding genomic regions and is hypothesized to impact regulatory elements that modulate gene expression. Here we present a statistically rigorous software tool GREGOR (Genomic Regulatory Elements and Gwas Overlap algoRithm) for evaluating enrichment of any set of genetic variants with any set of regulatory features. Using variants from five phenotypes, we describe a data-driven approach to determine the tissue and cell types most relevant to a trait of interest and to identify the subset of regulatory features likely impacted by these variants. Last, we experimentally evaluate six predicted functional variants at six lipid-associated loci and demonstrate significant evidence for allele-specific impact on expression levels. GREGOR systematically evaluates enrichment of genetic variation with the vast collection of regulatory data available to explore novel biological mechanisms of disease and guide us toward the functional variant at trait-associated loci. AVAILABILITY AND IMPLEMENTATION: GREGOR, including source code, documentation, examples, and executables, is available at http://genome.sph.umich.edu/wiki/GREGOR. CONTACT: cristen@umich.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Epigenômica , Variação Genética/genética , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Sequências Reguladoras de Ácido Nucleico/genética , Software , Genômica/métodos , Humanos , Especificidade de Órgãos , Fenótipo , Linguagens de Programação
17.
Nature ; 518(7538): 187-196, 2015 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-25673412

RESUMO

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.


Assuntos
Tecido Adiposo/metabolismo , Distribuição da Gordura Corporal , Estudo de Associação Genômica Ampla , Insulina/metabolismo , Locos de Características Quantitativas/genética , Adipócitos/metabolismo , Adipogenia/genética , Fatores Etários , Índice de Massa Corporal , Grupos de Populações Continentais/genética , Epigênese Genética , Europa (Continente)/etnologia , Feminino , Genoma Humano/genética , Humanos , Resistência à Insulina/genética , Masculino , Modelos Biológicos , Neovascularização Fisiológica/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único/genética , Caracteres Sexuais , Transcrição Genética/genética , Relação Cintura-Quadril
18.
Nature ; 518(7538): 197-206, 2015 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-25673413

RESUMO

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.


Assuntos
Índice de Massa Corporal , Estudo de Associação Genômica Ampla , Obesidade/genética , Obesidade/metabolismo , Adipogenia/genética , Adiposidade/genética , Fatores Etários , Grupos de Populações Continentais/genética , Metabolismo Energético/genética , Europa (Continente)/etnologia , Feminino , Predisposição Genética para Doença/genética , Ácido Glutâmico/metabolismo , Humanos , Insulina/metabolismo , Masculino , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Sinapses/metabolismo
19.
Nat Genet ; 46(4): 345-51, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24633158

RESUMO

Blood lipid levels are heritable, treatable risk factors for cardiovascular disease. We systematically assessed genome-wide coding variation to identify new genes influencing lipid traits, fine map known lipid loci and evaluate whether low-frequency variants with large effects exist for these traits. Using an exome array, we genotyped 80,137 coding variants in 5,643 Norwegians. We followed up 18 variants in 4,666 Norwegians and identified ten loci with coding variants associated with a lipid trait (P < 5 × 10(-8)). One variant in TM6SF2 (encoding p.Glu167Lys), residing in a known genome-wide association study locus for lipid traits, influences total cholesterol levels and is associated with myocardial infarction. Transient TM6SF2 overexpression or knockdown of Tm6sf2 in mice alters serum lipid profiles, consistent with the association observed in humans, identifying TM6SF2 as a functional gene within a locus previously known as NCAN-CILP2-PBX4 or 19p13. This study demonstrates that systematic assessment of coding variation can quickly point to a candidate causal gene.


Assuntos
Variação Genética , Lipídeos/sangue , Proteínas de Membrana/genética , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/genética , Animais , LDL-Colesterol/sangue , LDL-Colesterol/genética , Exoma/genética , Técnicas de Silenciamento de Genes , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Lipídeos/genética , Camundongos , Camundongos Endogâmicos C57BL , Mutação de Sentido Incorreto/genética , Noruega/epidemiologia , Fatores de Risco
20.
Am J Hum Genet ; 94(2): 233-45, 2014 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-24507775

RESUMO

Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.


Assuntos
LDL-Colesterol/genética , Exoma , Frequência do Gene , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Apolipoproteínas E/sangue , Apolipoproteínas E/genética , Estudos de Coortes , Dislipidemias/sangue , Dislipidemias/genética , Feminino , Seguimentos , Código Genético , Genótipo , Humanos , Lipase/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Pró-Proteína Convertase 9 , Pró-Proteína Convertases/genética , Receptores de LDL/genética , Análise de Sequência de DNA , Serina Endopeptidases/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA