Muhammad Ayub - Academia.edu (original) (raw)

Papers by Muhammad Ayub

Research paper thumbnail of Major depression in a large family in Pakistan: no relationship to inbreeding, economic status or rural living

Research paper thumbnail of A survey of knowledge and attitude of the general public towards epilepsy in Lahore, Pakistan

Objective: To explore the ideas people have towards epilepsy. Design: The qualitative methods wer... more Objective: To explore the ideas people have towards epilepsy. Design: The qualitative methods were used in the first step while in second stage a cross sectional design was used.

Research paper thumbnail of CC2D2A Gene Mutations Associated with Joubert Syndrome and Diagnostic Methods for Identifying the Same

Research paper thumbnail of Oligodentia and LTBP3

Research paper thumbnail of Genetic Studies of Bipolar Disorder in large Pakistani families

Research paper thumbnail of Whole Genome Sequencing in Large Pakistani Families with Mental Illness

Research paper thumbnail of The UK10K project identifies rare variants in health and disease

Nature, 2015

The contribution of rare and low-frequency variants to human traits is largely unexplored. Here w... more The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results. Assessment of the contribution of rare genetic variation to many human traits is still largely incomplete. In common and complex diseases, a lack of empirical data has to date hampered the systematic assessment of the contribution of rare and low-frequency genetic variants (defined throughout this paper as minor allele frequency (MAF) <1% and 1-5%, respectively). Rare variants are incompletely represented in genome-wide association (GWA) studies 1 and custom genotyping arrays 2,3 , and impute poorly with current reference panels. Rare and low-frequency variants also tend to be population-or sample-specific, requiring direct ascertainment through resequencing 4,5. Recent exome-wide resequencing studies have begun to explore the contribution of rare coding variants to complex traits 6 , but comparatively little is known of the non-coding part of the genome where most complex trait-associated loci lie 7. At the other end of the human disease spectrum, the widespread application of exome-wide sequencing is accelerating the rate at which genes and variants causal for rare diseases are being identified. Despite this, many Mendelian diseases still lack a genetic diagnosis and the penetrance of apparently disease-causing loci remains inadequately assessed.

Research paper thumbnail of Mutations in DCPS and EDC3 in Autosomal Recessive Intellectual Disability Indicate a Crucial Role for mRNA Decapping in Neurodevelopment

Human molecular genetics, Jan 20, 2015

There are two known mRNA degradation pathways, 3' to…

Research paper thumbnail of Rate and predictors of psychotic symptoms after Kashmir earthquake

European Archives of Psychiatry and Clinical Neuroscience, 2014

Research paper thumbnail of Psychiatric morbidity among Afghan refugees in Peshawar, Pakistan

Journal of Ayub Medical College, Abbottabad : JAMC

A review of the literature shows that refugees in different parts of the world have high rates of... more A review of the literature shows that refugees in different parts of the world have high rates of psychological and emotional problems. However, psychiatric morbidity among Afghan refugees in Pakistan has been poorly studied. Most of the studies of psychiatric disorders come from western countries. However, these studies may not be representative of the Afghan refugees in Pakistan. This study was carried out to measure psychiatric morbidity among a group of Afghan refugees attending a psychiatric clinic in Peshawar, Pakistan. This is a cross sectional study, to measure prevalence of psychiatric morbidity among the residents of Afghan refugee camps in Peshawar, Pakistan, who attended a psychiatric clinic between November 2003 and February 2004. Data were collected using Mini International neuropsychiatry Interview Schedule (MINI), and a form specifically developed for the study. Nearly 80% of our patients had a diagnosis of Post Traumatic Stress Disorder. Nearly half (47.9%) reported...

Research paper thumbnail of Psychiatric problems in an Afghan village

Journal of Ayub Medical College, Abbottabad : JAMC

The rates of psychiatric disorders might be very high in Afghanistan. The country has faced many ... more The rates of psychiatric disorders might be very high in Afghanistan. The country has faced many years of war and violence and therefore this is hardly surprising. We are describing the results of a community survey conducted by clinicians in a small village of Eastern Afghanistan. This study was carried out to measure prevalence of psychiatric disorders among the people living in a small village in the Nangerhar, Afghanistan. We also wanted to measure the associated demographic variables. A structured interview schedule, Mini International neuropsychiatry Interview Schedule (MINI), was used to measure psychiatric morbidity. More than 70% of the population fulfilled criteria for some form of mental illness. The rates of mental health problems are very high in Afghanistan. Any efforts to rebuild this war torn country should take sufficient measures in building mental health services with special emphasis on mental health problems.

Research paper thumbnail of Biallelic Truncating Mutations in FMN2, Encoding the Actin-Regulatory Protein Formin 2, Cause Nonsyndromic Autosomal-Recessive Intellectual Disability

The American Journal of Human Genetics, 2014

Research paper thumbnail of Angry Wives, Abusive Husbands: Relationship Between Domestic Violence and Psychosocial Variables

Women's Health Issues, 2008

Research paper thumbnail of Linkage Analysis in a Large Family from Pakistan with Depression and a High Incidence of Consanguineous Marriages

Human Heredity, 2008

A genome wide scan for linkage was performed in a five generation family with a high incidence of... more A genome wide scan for linkage was performed in a five generation family with a high incidence of depression and high average coefficient of inbreeding ascertained in a rural area of Pakistan. The effect of inbreeding on linkage analysis in an extended pedigree is discussed. 372 microsatellite markers were used in a genome wide linkage study. Inbreeding coefficients were measured by two methods using both genealogical and genotype data. Of 111 family members with phenotypic information, 82 were diagnosed with recurrent major depression. Linkage analysis using the program Superlink online generated LOD scores of less than one at all loci. A model free analysis with SimWalk did not result in any significant linkage score. The mean inbreeding coefficient was 0.038 estimated from genealogical data and 0.02 estimated from the genotype data. These results did not differ significantly. The effects of inbreeding included a reduction in the polymorphism information content of markers and an overestimate of marker allele frequencies. The analysis of very large families is computationally demanding. Problems encountered in this analysis, including loss of power due to reduced polymorphism information content and sensitivity of the LOD score method to estimates of allele frequencies, severely limited the chance of detecting linkage.

Research paper thumbnail of Etiology, Psychological Morbidity and Associated Impairments in Severe Mental Retardation

Research paper thumbnail of A Comparison of the Knowledge of Psychiatric Problems Among Medical Students, Doctors and University Teachers and Students In Lahore, Pakistan

JPPS, 2007

Objectives: Comparison of the medical and non-medical group for the knowledge of mental illness a... more Objectives: Comparison of the medical and non-medical group for the knowledge of mental illness and its treatment. Design: Cross sectional study. Place and duration of study: The study was conducted between March to september 2004 in two medical colleges and their attached ...

Research paper thumbnail of Oligodontia Is Caused by Mutation in LTBP3, the Gene Encoding Latent TGF-β Binding Protein 3

The American Journal of Human Genetics, 2009

We have identified a consanguineous Pakistani family where oligodontia is inherited along with sh... more We have identified a consanguineous Pakistani family where oligodontia is inherited along with short stature in an autosomal-recessive fashion. Increased bone density was present in the spine and at the base of the skull. Using high-density single-nucleotide polymorphism microarrays for homozygosity mapping, we identified a 28 Mb homozygous stretch shared between affected individuals on chromosome 11q13. Screening selected candidate genes within this region, we identified a homozygous nonsense mutation, Y774X, within LTBP3, the gene for the latent TGF-b binding protein 3, an extracellular matrix protein believed to be required for osteoclast function.

Research paper thumbnail of Mutation in NSUN2, which Encodes an RNA Methyltransferase, Causes Autosomal-Recessive Intellectual Disability

The American Journal of Human Genetics, 2012

The full-text may be used and/or reproduced, and given to third parties in any format or medium, ... more The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.

Research paper thumbnail of Psychologists experience of cognitive behaviour therapy in a developing country: a qualitative study from Pakistan

Background: Psychological therapies especially Cognitive Behaviour Therapy (CBT) are used widely ... more Background: Psychological therapies especially Cognitive Behaviour Therapy (CBT) are used widely in the West to help patients with psychiatric problems. Cognitive Behaviour Therapy has an established evidence base for the treatment of different emotional disorders. In spite of these developments in the developed world, patients in most developing countries hardly benefit from non pharmacological interventions. Although a significant number of psychologists are trained in Pakistan each year, psychological interventions play only a minor role in treatment plans in Pakistan. We conducted interviews with psychologists in Pakistan, to explore their experiences and their views on "providing CBT in Pakistan". These interviews were conducted as part of a project whose focus was to try to develop culturally-sensitive CBT in Pakistan. Methods: In depth semi structured interviews were conducted with 5 psychologists working in psychiatry departments in Lahore, Pakistan. Results: All the psychologists reported that psychotherapies, including CBT, need adjustments for use in Pakistan, although they were not able to elicit on these in details. Four major themes were discovered, hurdles in therapy, therapy related issues, involvement of the family and modification in therapy. The biggest hurdles in therapy were described to be service and resource issues. Conclusions: For CBT to be acceptable, accessible and effective in Non Western cultures numerous adjustments need to be made, taking into consideration; factors related to service structure and delivery, patient's knowledge and beliefs about health and the therapy itself. Interviews with the psychologists in these countries can give us insights which can guide development of therapy and manuals to support its delivery.

Research paper thumbnail of Major depression in a large family in Pakistan: no relationship to inbreeding, economic status or rural living

Research paper thumbnail of A survey of knowledge and attitude of the general public towards epilepsy in Lahore, Pakistan

Objective: To explore the ideas people have towards epilepsy. Design: The qualitative methods wer... more Objective: To explore the ideas people have towards epilepsy. Design: The qualitative methods were used in the first step while in second stage a cross sectional design was used.

Research paper thumbnail of CC2D2A Gene Mutations Associated with Joubert Syndrome and Diagnostic Methods for Identifying the Same

Research paper thumbnail of Oligodentia and LTBP3

Research paper thumbnail of Genetic Studies of Bipolar Disorder in large Pakistani families

Research paper thumbnail of Whole Genome Sequencing in Large Pakistani Families with Mental Illness

Research paper thumbnail of The UK10K project identifies rare variants in health and disease

Nature, 2015

The contribution of rare and low-frequency variants to human traits is largely unexplored. Here w... more The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results. Assessment of the contribution of rare genetic variation to many human traits is still largely incomplete. In common and complex diseases, a lack of empirical data has to date hampered the systematic assessment of the contribution of rare and low-frequency genetic variants (defined throughout this paper as minor allele frequency (MAF) <1% and 1-5%, respectively). Rare variants are incompletely represented in genome-wide association (GWA) studies 1 and custom genotyping arrays 2,3 , and impute poorly with current reference panels. Rare and low-frequency variants also tend to be population-or sample-specific, requiring direct ascertainment through resequencing 4,5. Recent exome-wide resequencing studies have begun to explore the contribution of rare coding variants to complex traits 6 , but comparatively little is known of the non-coding part of the genome where most complex trait-associated loci lie 7. At the other end of the human disease spectrum, the widespread application of exome-wide sequencing is accelerating the rate at which genes and variants causal for rare diseases are being identified. Despite this, many Mendelian diseases still lack a genetic diagnosis and the penetrance of apparently disease-causing loci remains inadequately assessed.

Research paper thumbnail of Mutations in DCPS and EDC3 in Autosomal Recessive Intellectual Disability Indicate a Crucial Role for mRNA Decapping in Neurodevelopment

Human molecular genetics, Jan 20, 2015

There are two known mRNA degradation pathways, 3' to…

Research paper thumbnail of Rate and predictors of psychotic symptoms after Kashmir earthquake

European Archives of Psychiatry and Clinical Neuroscience, 2014

Research paper thumbnail of Psychiatric morbidity among Afghan refugees in Peshawar, Pakistan

Journal of Ayub Medical College, Abbottabad : JAMC

A review of the literature shows that refugees in different parts of the world have high rates of... more A review of the literature shows that refugees in different parts of the world have high rates of psychological and emotional problems. However, psychiatric morbidity among Afghan refugees in Pakistan has been poorly studied. Most of the studies of psychiatric disorders come from western countries. However, these studies may not be representative of the Afghan refugees in Pakistan. This study was carried out to measure psychiatric morbidity among a group of Afghan refugees attending a psychiatric clinic in Peshawar, Pakistan. This is a cross sectional study, to measure prevalence of psychiatric morbidity among the residents of Afghan refugee camps in Peshawar, Pakistan, who attended a psychiatric clinic between November 2003 and February 2004. Data were collected using Mini International neuropsychiatry Interview Schedule (MINI), and a form specifically developed for the study. Nearly 80% of our patients had a diagnosis of Post Traumatic Stress Disorder. Nearly half (47.9%) reported...

Research paper thumbnail of Psychiatric problems in an Afghan village

Journal of Ayub Medical College, Abbottabad : JAMC

The rates of psychiatric disorders might be very high in Afghanistan. The country has faced many ... more The rates of psychiatric disorders might be very high in Afghanistan. The country has faced many years of war and violence and therefore this is hardly surprising. We are describing the results of a community survey conducted by clinicians in a small village of Eastern Afghanistan. This study was carried out to measure prevalence of psychiatric disorders among the people living in a small village in the Nangerhar, Afghanistan. We also wanted to measure the associated demographic variables. A structured interview schedule, Mini International neuropsychiatry Interview Schedule (MINI), was used to measure psychiatric morbidity. More than 70% of the population fulfilled criteria for some form of mental illness. The rates of mental health problems are very high in Afghanistan. Any efforts to rebuild this war torn country should take sufficient measures in building mental health services with special emphasis on mental health problems.

Research paper thumbnail of Biallelic Truncating Mutations in FMN2, Encoding the Actin-Regulatory Protein Formin 2, Cause Nonsyndromic Autosomal-Recessive Intellectual Disability

The American Journal of Human Genetics, 2014

Research paper thumbnail of Angry Wives, Abusive Husbands: Relationship Between Domestic Violence and Psychosocial Variables

Women's Health Issues, 2008

Research paper thumbnail of Linkage Analysis in a Large Family from Pakistan with Depression and a High Incidence of Consanguineous Marriages

Human Heredity, 2008

A genome wide scan for linkage was performed in a five generation family with a high incidence of... more A genome wide scan for linkage was performed in a five generation family with a high incidence of depression and high average coefficient of inbreeding ascertained in a rural area of Pakistan. The effect of inbreeding on linkage analysis in an extended pedigree is discussed. 372 microsatellite markers were used in a genome wide linkage study. Inbreeding coefficients were measured by two methods using both genealogical and genotype data. Of 111 family members with phenotypic information, 82 were diagnosed with recurrent major depression. Linkage analysis using the program Superlink online generated LOD scores of less than one at all loci. A model free analysis with SimWalk did not result in any significant linkage score. The mean inbreeding coefficient was 0.038 estimated from genealogical data and 0.02 estimated from the genotype data. These results did not differ significantly. The effects of inbreeding included a reduction in the polymorphism information content of markers and an overestimate of marker allele frequencies. The analysis of very large families is computationally demanding. Problems encountered in this analysis, including loss of power due to reduced polymorphism information content and sensitivity of the LOD score method to estimates of allele frequencies, severely limited the chance of detecting linkage.

Research paper thumbnail of Etiology, Psychological Morbidity and Associated Impairments in Severe Mental Retardation

Research paper thumbnail of A Comparison of the Knowledge of Psychiatric Problems Among Medical Students, Doctors and University Teachers and Students In Lahore, Pakistan

JPPS, 2007

Objectives: Comparison of the medical and non-medical group for the knowledge of mental illness a... more Objectives: Comparison of the medical and non-medical group for the knowledge of mental illness and its treatment. Design: Cross sectional study. Place and duration of study: The study was conducted between March to september 2004 in two medical colleges and their attached ...

Research paper thumbnail of Oligodontia Is Caused by Mutation in LTBP3, the Gene Encoding Latent TGF-β Binding Protein 3

The American Journal of Human Genetics, 2009

We have identified a consanguineous Pakistani family where oligodontia is inherited along with sh... more We have identified a consanguineous Pakistani family where oligodontia is inherited along with short stature in an autosomal-recessive fashion. Increased bone density was present in the spine and at the base of the skull. Using high-density single-nucleotide polymorphism microarrays for homozygosity mapping, we identified a 28 Mb homozygous stretch shared between affected individuals on chromosome 11q13. Screening selected candidate genes within this region, we identified a homozygous nonsense mutation, Y774X, within LTBP3, the gene for the latent TGF-b binding protein 3, an extracellular matrix protein believed to be required for osteoclast function.

Research paper thumbnail of Mutation in NSUN2, which Encodes an RNA Methyltransferase, Causes Autosomal-Recessive Intellectual Disability

The American Journal of Human Genetics, 2012

The full-text may be used and/or reproduced, and given to third parties in any format or medium, ... more The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.

Research paper thumbnail of Psychologists experience of cognitive behaviour therapy in a developing country: a qualitative study from Pakistan

Background: Psychological therapies especially Cognitive Behaviour Therapy (CBT) are used widely ... more Background: Psychological therapies especially Cognitive Behaviour Therapy (CBT) are used widely in the West to help patients with psychiatric problems. Cognitive Behaviour Therapy has an established evidence base for the treatment of different emotional disorders. In spite of these developments in the developed world, patients in most developing countries hardly benefit from non pharmacological interventions. Although a significant number of psychologists are trained in Pakistan each year, psychological interventions play only a minor role in treatment plans in Pakistan. We conducted interviews with psychologists in Pakistan, to explore their experiences and their views on "providing CBT in Pakistan". These interviews were conducted as part of a project whose focus was to try to develop culturally-sensitive CBT in Pakistan. Methods: In depth semi structured interviews were conducted with 5 psychologists working in psychiatry departments in Lahore, Pakistan. Results: All the psychologists reported that psychotherapies, including CBT, need adjustments for use in Pakistan, although they were not able to elicit on these in details. Four major themes were discovered, hurdles in therapy, therapy related issues, involvement of the family and modification in therapy. The biggest hurdles in therapy were described to be service and resource issues. Conclusions: For CBT to be acceptable, accessible and effective in Non Western cultures numerous adjustments need to be made, taking into consideration; factors related to service structure and delivery, patient's knowledge and beliefs about health and the therapy itself. Interviews with the psychologists in these countries can give us insights which can guide development of therapy and manuals to support its delivery.