Association of Genetic Variants With Migraine Subclassified by Clinical Symptoms in Adult Females

Migraine is heritable and formally diagnosed by structured criteria that require presence of some but not all possible migraine symptoms which include aura, several distinct manifestations of pain, nausea/vomiting, and sensitivity to light or sound. The most recent genome-wide genetic association study (GWAS) for migraine identified 38 loci. We investigated whether 46 single-nucleotide polymorphisms (SNPs), i.e., genetic variants, at these loci may have especially pronounced, i.e., selective, association with migraine presenting with individual symptoms compared to absence of migraine. Selective genetic associations of SNPs were evaluated through a likelihood framework in the Women's Genome Health Study (WGHS), a population-based cohort of middle-aged women including 3,003 experiencing migraine and 18,108 not experiencing migraine, all with genetic information. SNPs at 12 loci displayed significant selective association for migraine subclassified by specific symptoms, among which six selective associations are novel. Symptoms showing selective association include aura, nausea/vomiting, photophobia, and phonophobia. The selective associations were consistent whether the women met all formal criteria for diagnostic for migraine or lacked one of the diagnostic criteria, formally termed probable migraine. Subsequently, we performed latent class analysis of migraine diagnostic symptoms among 69,861 women experiencing migraine from the WGHS recruitment sample to assess whether there were clusters of specific symptoms that might also have a genetic basis. However, no globally robust latent migraine substructures of diagnostic symptoms were observed nor were there selective genetic associations with specific combinations of symptoms revealed among weakly supported latent classes. The findings extend previously reported selective genetic associations with migraine diagnostic symptoms while supporting models for shared genetic susceptibility across all qualifying migraine at many loci.

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Gene-centric association signals for haemostasis and thrombosis traits identified with the HumanCVD BeadChip

Thrombosis and Haemostasis ◽

10.1160/th13-02-0087 ◽

2013 ◽

Vol 110 (11) ◽

pp. 995-1003 ◽

Cited By ~ 7

Author(s):

Sonia Shah ◽

Anna Guyatt ◽

Christophe Ladroue ◽

Meena Kumari ◽

Fotios Drenos ◽

...

Keyword(s):

Platelet Count ◽

Genetic Variants ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Pleiotropic Effect ◽

Plasma Viscosity ◽

Factor Vii ◽

Health Study ◽

Nucleotide Polymorphisms ◽

Genetic Associations

SummaryCoagulation phenotypes show strong intercorrelations, affect cardiovascular disease risk and are influenced by genetic variants. The objective of this study was to search for novel genetic variants influencing the following coagulation phenotypes: factor VII levels, fibrinogen levels, plasma viscosity and platelet count. We genotyped the British Women’s Heart and Health Study (n=3,445) and the Whitehall II study (n=5,059) using the Illumina HumanCVD BeadArray to investigate genetic associations and pleiotropy. In addition to previously reported associations (SH2B3, F7/F10, PROCR, GCKR, FGA/FGB/FGG, IL5), we identified novel associations at GRK5 (rs10128498, p = 1.30×10−6), GCKR (rs1260326, p = 1.63×10−6), ZNF259-APOA5 (rs651821, p = 7.17x10–6) with plasma viscosity; and at CSF1 (rs333948, p = 8.88×10−6) with platelet count. A pleiotropic effect was identified in GCKR which associated with factor VII (p = 2.16×10−7) and plasma viscosity (p = 1.63×10−6), and, to a lesser extent, ZNF259-APOA5 which also associated with factor VII and fibrinogen (p<1.00×10−2) and plasma viscosity (p<1.00×10−5). Triglyceride associated variants were overrepresented in factor VII and plasma viscosity associations. Adjusting for triglyceride levels resulted in attenuation of associations at the GCKR and ZNF259-APOA5 loci. In addition to confirming previously reported associations, we identified four single nucleotide polymorphisms (SNPs) associated with plasma viscosity and platelet count and found evidence of pleiotropic effects with SNPs in GCKR and ZNF259-APOA5. These triglyceride-associated, pleiotropic SNPs suggest a possible causal role for triglycerides in coagulation.

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Symptom patterns in childhood arterial ischemic stroke: Analysis of a population-based study in Germany

Klinische Pädiatrie ◽

10.1055/a-0684-9794 ◽

2018 ◽

Vol 230 (06) ◽

pp. 319-325

Author(s):

Lucia Gerstl ◽

Raphael Weinberger ◽

Rüdiger von Kries ◽

Florian Heinen ◽

Andreas Sebastian Schroeder ◽

...

Keyword(s):

Ischemic Stroke ◽

Clinical Symptoms ◽

Population Based ◽

Case Definition ◽

Childhood Stroke ◽

Older Children ◽

Arterial Ischemic Stroke ◽

Focal Neurological Deficit ◽

Symptom Patterns ◽

Specific Symptoms

Hintergrund Die zeitliche Verzögerung zwischen Symptombeginn und Diagnose ist eine Herausforderung in der Behandlung von Kindern mit arteriell ischämischem Schlaganfall. Frühere Studien zur klinischen Präsentation beschäftigten sich v. a. mit kumulativen Symptomen. Zielsetzung Ziel dieser Studie ist es, mögliche Symptommuster aufzuzeigen. Methoden In einer aktiven Beobachtungsstudie zwischen 01/2015 und 12/2016 (ESPED-Studie) wurden Kinder mit Erstdiagnose eines arteriell ischämischen Schlaganfalls eingeschlossen. Isoliert auftretende Erstsymptome wurden verschiedenen Symptomkombinationen gegenübergestellt. Zudem wurde untersucht, inwieweit ein als „akut“ oder „progredient“ klassifiziertes Auftreten der Symptome Rückschlüsse auf die zugrundeliegende Ätiologie erlaubt. Ergebnisse Es wurden 99 Kinder in die Studie eingeschlossen. Unabhängig vom Alter traten überwiegend fokale Symptome auf (86%). Krampfanfälle als Initialsymptom wurden insbesondere bei Säuglingen beschrieben (67%), wohin-gegen diffuse, unspezifische Symptome vor allem bei Vorschulkindern (38%) und älteren Kindern (59%) auftraten. Isoliert traten fokale Symptome bei 37 Kindern auf, 48 Kinder zeigten zusätzlich unspezifische Symptome, darunter auch 9 Kinder mit Krampfanfällen. Isolierte unspezifische Symptome zeigten sich lediglich bei 7 Kindern, 2 Kinder wurden nur mit Krampfanfällen symptomatisch. Die Akuität des Symptombeginns wurde bei 53/78 als „akut“ und bei “25/78 Fällen als „progredient“ klassifiziert, lieferte jedoch keinen Hinweis auf die zugrundeliegende Ätiologie. Schlussfolgerung Jedes neue fokal neurologische Defizit sollte unabhängig vom Auftreten (isoliert oder kombiniert, akut oder progredient) an einen kindlichen Schlaganfall denken lassen. Background Time delay between onset of clinical symptoms and diagnosis is a challenge in childhood arterial ischemic stroke. Most previous studies reported cumulative symptoms. Objective We attempted to identify typical symptom patterns and assessed their emergence in childhood stroke. Methods Prospective active surveillance in ESPED, a hospital based Pediatric Surveillance Unit for rare diseases in Germany, between January 2015 and December 2016. Case definition: first diagnosis of a radiologically confirmed arterial ischemic stroke. Symptom patterns were identified as occurring in isolation or in combination. We distinguished acute vs. progressive onset. We ascertained risk factors to identify the possible etiology. Results 99 children with childhood arterial ischemic stroke were reported. Focal symptoms were the predominant presenting feature (86%), independent of age. Seizures were more often seen in infants < 1 year (67%), whereas diffuse symptoms were more present in pre-school children (38%) and older children (59%). 37 children had focal features alone and 48 additional non-specific features, including 9 with seizures. Isolated non-specific features accounted for 7 cases, and 2 children had (focal) seizures as the only symptom. In 77% of all cases at least one risk factor was identified. The emergence of symptoms was acute in 53/78 cases and progressive in 25/78 cases. The pattern of emergence was unrelated to the underlying etiology. Conclusions Any new focal neurological deficit in isolation, or associated with seizures or further non-specific symptoms should alert to childhood stroke.

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Candidate gene scan for Single Nucleotide Polymorphisms involved in the determination of normal variability in human craniofacial morphology

10.1101/060814 ◽

2016 ◽

Author(s):

Mark Barash ◽

Philipp E. Bayer ◽

Angela van Daal

Keyword(s):

Single Nucleotide Polymorphisms ◽

Candidate Gene ◽

Genetic Variants ◽

Massively Parallel Sequencing ◽

Craniofacial Morphology ◽

Candidate Gene Approach ◽

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Single Nucleotide ◽

Genome Wide

AbstractDespite intensive research on genetics of the craniofacial morphology using animal models and human craniofacial syndromes, the genetic variation that underpins normal human facial appearance is still largely elusive. Recent development of novel digital methods for capturing the complexity of craniofacial morphology in conjunction with high-throughput genotyping methods, show great promise for unravelling the genetic basis of such a complex trait.As a part of our efforts on detecting genomic variants affecting normal craniofacial appearance, we have implemented a candidate gene approach by selecting 1,201 single nucleotide polymorphisms (SNPs) and 4,732 tag SNPs in over 170 candidate genes and intergenic regions. We used 3-dimentional (3D) facial scans and direct cranial measurements of 587 volunteers to calculate 104 craniofacial phenotypes. Following genotyping by massively parallel sequencing, genetic associations between 2,332 genetic markers and 104 craniofacial phenotypes were tested.An application of a Bonferroni–corrected genome–wide significance threshold produced significant associations between five craniofacial traits and six SNPs. Specifically, associations of nasal width with rs8035124 (15q26.1), cephalic index with rs16830498 (2q23.3), nasal index with rs37369 (5q13.2), transverse nasal prominence angle with rs59037879 (10p11.23) and rs10512572 (17q24.3), and principal component explaining 73.3% of all the craniofacial phenotypes, with rs37369 (5p13.2) and rs390345 (14q31.3) were observed.Due to over-conservative nature of the Bonferroni correction, we also report all the associations that reached the traditional genome-wide p-value threshold (<5.00E-08) as suggestive. Based on the genome-wide threshold, 8 craniofacial phenotypes demonstrated significant associations with 34 intergenic and extragenic SNPs. The majority of associations are novel, except PAX3 and COL11A1 genes, which were previously reported to affect normal craniofacial variation.This study identified the largest number of genetic variants associated with normal variation of craniofacial morphology to date by using a candidate gene approach, including confirmation of the two previously reported genes. These results enhance our understanding of the genetics that determines normal variation in craniofacial morphology and will be of particular value in medical and forensic fields.Author SummaryThere is a remarkable variety of human facial appearances, almost exclusively the result of genetic differences, as exemplified by the striking resemblance of identical twins. However, the genes and specific genetic variants that affect the size and shape of the cranium and the soft facial tissue features are largely unknown. Numerous studies on animal models and human craniofacial disorders have identified a large number of genes, which may regulate normal craniofacial embryonic development.In this study we implemented a targeted candidate gene approach to select more than 1,200 polymorphisms in over 170 genes that are likely to be involved in craniofacial development and morphology. These markers were genotyped in 587 DNA samples using massively parallel sequencing and analysed for association with 104 traits generated from 3-dimensional facial images and direct craniofacial measurements. Genetic associations (p-values<5.00E-08) were observed between 8 craniofacial traits and 34 single nucleotide polymorphisms (SNPs), including two previously described genes and 26 novel candidate genes and intergenic regions. This comprehensive candidate gene study has uncovered the largest number of novel genetic variants affecting normal facial appearance to date. These results will appreciably extend our understanding of the normal and abnormal embryonic development and impact our ability to predict the appearance of an individual from a DNA sample in forensic criminal investigations and missing person cases.

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Genetic Variants behind Cardiovascular Diseases and Dementia

Genes ◽

10.3390/genes11121514 ◽

2020 ◽

Vol 11 (12) ◽

pp. 1514

Author(s):

Wei-Min Ho ◽

Yah-Yuan Wu ◽

Yi-Chun Chen

Keyword(s):

White Matter ◽

Cardiovascular Diseases ◽

Genetic Variants ◽

White Matter Hyperintensities ◽

Association Studies ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Pubmed Database ◽

Risk Snps

Cardiovascular diseases (CVDs) and dementia are the leading causes of disability and mortality. Genetic connections between cardiovascular risk factors and dementia have not been elucidated. We conducted a scoping review and pathway analysis to reveal the genetic associations underlying both CVDs and dementia. In the PubMed database, literature was searched using keywords associated with diabetes mellitus, hypertension, dyslipidemia, white matter hyperintensities, cerebral microbleeds, and covert infarctions. Gene lists were extracted from these publications to identify shared genes and pathways for each group. This included high penetrance genes and single nucleotide polymorphisms (SNPs) identified through genome wide association studies. Most risk SNPs to both diabetes and dementia participate in the phospholipase C enzyme system and the downstream nositol 1,4,5-trisphosphate and diacylglycerol activities. Interestingly, AP-2 (TFAP2) transcription factor family and metabolism of vitamins and cofactors were associated with genetic variants that were shared by white matter hyperintensities and dementia, and by microbleeds and dementia. Variants shared by covert infarctions and dementia were related to VEGF ligand–receptor interactions and anti-inflammatory cytokine pathways. Our review sheds light on future investigations into the causative relationships behind CVDs and dementia, and can be a paradigm of the identification of dementia treatments.

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PSI-18 Identifying genetic variants associated with grazing, walking, and slope use of cattle experiencing mild heat load

Journal of Animal Science ◽

10.1093/jas/skab235.516 ◽

2021 ◽

Vol 99 (Supplement_3) ◽

pp. 281-281

Author(s):

Morgan R Stegemiller ◽

Melinda J Ellison ◽

John B Hall ◽

James E Sprinkle ◽

Brenda M Murdoch

Keyword(s):

Heat Stress ◽

Genetic Variants ◽

Heat Load ◽

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Chromosome 11 ◽

Maximum Slope ◽

Grazing Behavior ◽

Mild Heat ◽

Walking Time

Abstract Rangeland is a valuable resource that can allow producers to cost effectively provide nutrients for grazing cattle. However, grazing behavior of cattle is adversely affected when the temperature humidity index is greater than 72. It is possible to select cattle that exhibit efficient grazing behavior even under mild heat stress. This study evaluated genetic associations with grazing behavior to help producers identify cows that will effectively use their rangeland pastures. Using genome-wide associations, this study identified single nucleotide polymorphisms (SNPs) associated with grazing time, walking time and max slope that cattle utilized while experiencing mild heat load. Data were collected from Angus X Hereford 2-year-old beef cows from UI herd over two years (37 grazing and walking minutes, 38 max slope). Genotypes were obtained using a Bovine GGP 50K SNP marker array and 41,686 markers were used in the analyses. Two SNPs on chromosome 11 are significantly (P = 5.01e-7, P = 6.46e-7) associated with grazing minutes and explain 0.52 proportion of variance (PVE). A SNP on chromosome 3 is significant for walking minutes (P=1.91e-6) with a PVE of 0.48. Additionally, a SNP on chromosome 14 is significantly (P = 8.50e-6) associated with max slope and has a PVE of 0.43. This ongoing project identified significant associations with grazing and walking minutes and maximum slope. This research will be strengthened with the addition of more animals over successive years. Some cattle spend more time grazing, walking, or at a higher elevation in mild heat load. Identifying genetic variants associated with grazing time, walking time, and maximum slope use while under heat stress can enable producers to select for cattle that best fit the rangeland available to them.

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PNPLA3 Polymorphisms and Liver Aminotransferase Levels in a Mexican American Population

Clinical & Investigative Medicine ◽

10.25011/cim.v35i4.17153 ◽

2012 ◽

Vol 35 (4) ◽

pp. 237 ◽

Cited By ~ 20

Author(s):

Quan Li ◽

Hui-Qi Qu ◽

Anne R. Rentfro ◽

Megan L. Grove ◽

Shaper Mirza ◽

...

Keyword(s):

Genetic Association ◽

Mexican Americans ◽

Mexican American ◽

Population Based ◽

Nucleotide Polymorphisms ◽

American Population ◽

Genetic Associations ◽

The Metabolic Syndrome ◽

Elevated Liver Enzymes ◽

Mexican American Population

Purpose: This study examined genetic associations of patatin-like phospholipase domain containing 3 gene (PNPLA3) polymorphisms and liver aminotransferases in an extensively documented, randomly recruited Mexican American population at high risk of liver disease. Methods: Two single nucleotide polymorphisms (SNP) in the PNPLA3 gene (i.e., rs738409 and rs2281135) were genotyped in 1532 individuals. Population stratification was corrected by the genotyping of 103 ancestry informative markers (AIMs) for Mexican Americans. Results: Both PNPLA3 SNPs showed highly significant association with alanine aminotransferase (ALT) levels, but was also, in males, associated with aspartate aminotransferase (AST) levels. Haplotypic association test of the two SNPs suggested stronger genetic association with rs738409 than rs2281135. Obvious sex effects were observed: rs738409-sex interaction in ALT levels P=8.37x10-4; rs738409-sex interaction in AST levels P=5.03x10-3. Conclusions: This population study highlights a sex-specific association of PNPLA3 polymorphisms and elevated liver enzymes in a population-based study, independent of common pathological factors of the metabolic syndrome. The strong genetic association found in women≤50 years old, but not in women > 50 years old, suggests that sex hormones may mediate the sex effect.

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NOVEL GENETIC SUSCEPTIBILITY CANDIDATES IN GRANULOMATOUS AND NON-GRANULOMATOUS PEDIATRIC CROHN’S DISEASE

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.071 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S30-S30

Author(s):

Allyson Hodgkins ◽

R Alan Harris ◽

Justin Qian ◽

Richard Kellermayer

Keyword(s):

Genetic Variation ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Large Population ◽

Population Based ◽

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Hla Dqa1

Abstract Background Non-caseating granulomas are a hallmark histopathological finding of Crohn’s disease (CD). Studies have suggested that the presence of granulomas may indicate a more aggressive CD phenotype associated with a complicated clinical course, including stricturing and/or penetrating disease, need for biologic therapy, and need for surgery. As such, identification of genetic associations of granulomatous CD (GCD) may help elucidate disease pathogenesis, which in turn may optimize treatments and guide novel therapeutics to combat CD complications. There is relatively sparse genetic information known about CD subtypes, especially GCD. The aim of this study was to determine the extent of genetic variation between pediatric CD patients with and without a pathognomonic sub-mucosal granuloma detected at the time of diagnosis. Methods Whole-exome next-generation sequencing (WES) was performed on peripheral blood derived DNA from patients with GCD and non-GCD (NGCD). PLINK analysis was used to identify single nucleotide polymorphisms (SNPs) that were overrepresented in comparisons between groups, and subgroup allele frequencies were also compared to publically available, large population-based genomic data in gnomAD. The potential deleteriousness of single nucleotide variants was determined by the CADD scoring tool. Results WES was completed for 17 patients with GCD and 19 with NGCD. There were no significant differences in baseline clinical characteristics, treatments, nor 1-year outcomes between the groups. Overlap analyses between PLINK- and gnomAD-generated SNPs revealed significant enrichment in those associated with HLA-DQA1, LILRA1, SAA2, PCDHB, HLA-B, NOD2, and IGH shared by GCD and NGCD groups. In the meantime, GCD-specific (top candidates linked with HLA-B and MUC4) and NGCD-specific (top candidates linked with HLA-B and ACOT9) SNPs were sparse. Conclusions We are the first to examine WES-based genetic variation between treatment-naïve pediatric CD patients purely separated by the presence of a sub-mucosal epithelioid granuloma. While there were very few SNPs consistently differentiating between GCD and NGCD patients in our cohort using two distinct methodologies, we were able to identify several novel SNPs that were significantly enriched in pediatric CD patients compared to the control human genome. Our findings will require subsequent confirmation in larger but similarly scrutinized cohorts of patients.

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Scrub typhus (Orientia tsutsugamushi), A rapidly spreading epidemic in Chennai - A standalone lab experience

International Journal of Bioassays ◽

10.21746/ijbio.2016.09.0021 ◽

2016 ◽

Vol 5 (09) ◽

pp. 4896

Author(s):

Sripriya C.S.* ◽

Shanthi B. ◽

Arockia Doss S. ◽

Antonie Raj I. ◽

Mohana Priya

Keyword(s):

Scrub Typhus ◽

Clinical Symptoms ◽

Clinical Manifestations ◽

Febrile Illness ◽

Orientia Tsutsugamushi ◽

The Past ◽

Igm Elisa ◽

The Mean ◽

Specific Symptoms ◽

Symptoms And Signs

Scrub typhus (Orientia tsutsugamushi), is a strict intracellular bacterium which is reported to be a recent threat to parts of southern India. There is re-emergence of scrub typhus during the past few years in Chennai. Scrub typhus is an acute febrile illness which generally causes non-specific symptoms and signs. The clinical manifestations of this disease range from sub-clinical disease to organ failure to fatal disease. This study documents our laboratory experience in diagnosis of scrub typhus in patients with fever and suspected clinical symptoms of scrub typhus infection for a period of two years from April 2014 to April 2016 using immunochromatography and IgM ELISA methods. The study was conducted on 648 patients out of whom 188 patients were found to be positive for scrub typhus. Results also showed that pediatric (0 -12 years) and young adults (20 – 39 years) were more exposed to scrub typhus infection and female patients were more infected compared to male. The study also showed that the rate of infection was higher between September to February which also suggested that the infection rate is proportional to the climatic condition. Statistical analysis showed that the mean age of the patients in this study was 37.6, standard deviation was 18.97, CV % was 50.45.

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Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers

Genes ◽

10.3390/genes12050686 ◽

2021 ◽

Vol 12 (5) ◽

pp. 686

Author(s):

Alireza Nazarian ◽

Alexander M. Kulminski

Keyword(s):

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Significance Level ◽

Association Analyses ◽

Complex Disorders ◽

Specific Effects ◽

Genome Wide ◽

Genetic Mechanisms ◽

Sex Disparities ◽

Almost All

Almost all complex disorders have manifested epidemiological and clinical sex disparities which might partially arise from sex-specific genetic mechanisms. Addressing such differences can be important from a precision medicine perspective which aims to make medical interventions more personalized and effective. We investigated sex-specific genetic associations with colorectal (CRCa) and lung (LCa) cancers using genome-wide single-nucleotide polymorphisms (SNPs) data from three independent datasets. The genome-wide association analyses revealed that 33 SNPs were associated with CRCa/LCa at P < 5.0 × 10−6 neither males or females. Of these, 26 SNPs had sex-specific effects as their effect sizes were statistically different between the two sexes at a Bonferroni-adjusted significance level of 0.0015. None had proxy SNPs within their ±1 Mb regions and the closest genes to 32 SNPs were not previously associated with the corresponding cancers. The pathway enrichment analyses demonstrated the associations of 35 pathways with CRCa or LCa which were mostly implicated in immune system responses, cell cycle, and chromosome stability. The significant pathways were mostly enriched in either males or females. Our findings provided novel insights into the potential sex-specific genetic heterogeneity of CRCa and LCa at SNP and pathway levels.

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Case–Parent Trio Studies in Cleft Lip and Palate

Global Medical Genetics ◽

10.1055/s-0040-1722097 ◽

2020 ◽

Vol 07 (03) ◽

pp. 075-079

Author(s):

Mahamad Irfanulla Khan ◽

Prashanth CS

Keyword(s):

Genetic Variants ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

Association Studies ◽

Geographical Location ◽

Genetic Association Studies ◽

Population Based ◽

Genome Wide Association Studies ◽

Family Based ◽

Study Designs

AbstractCleft lip with or without cleft palate (CL/P) is one of the most common congenital malformations in humans involving various genetic and environmental risk factors. The prevalence of CL/P varies according to geographical location, ethnicity, race, gender, and socioeconomic status, affecting approximately 1 in 800 live births worldwide. Genetic studies aim to understand the mechanisms contributory to a phenotype by measuring the association between genetic variants and also between genetic variants and phenotype population. Genome-wide association studies are standard tools used to discover genetic loci related to a trait of interest. Genetic association studies are generally divided into two main design types: population-based studies and family-based studies. The epidemiological population-based studies comprise unrelated individuals that directly compare the frequency of genetic variants between (usually independent) cases and controls. The alternative to population-based studies (case–control designs) includes various family-based study designs that comprise related individuals. An example of such a study is a case–parent trio design study, which is commonly employed in genetics to identify the variants underlying complex human disease where transmission of alleles from parents to offspring is studied. This article describes the fundamentals of case–parent trio study, trio design and its significances, statistical methods, and limitations of the trio studies.

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