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Posts Tagged ‘disease’

copd_smoking_nat_genet_lung_function_gwas_wain

We – as a group – carried out the largest genome-wide association study to identify genetic variants that are associated with decreased lung function and increased risk of chronic obstructive pulmonary disease. We hope that our findings will ultimately lead to the identification of effective drug targets for COPD. Image source: University of Leicester

I remember reading somewhere that ‘if you get asked the same question three times, then write a blog post about it’. That’s what I’ve been doing so far, and the purpose of this blog post is the same: to try and provide an answer to a commonly asked question. (Important note: my answers are in no way authoritative and only meant for interested non-scientists)

As a ‘Genetic Epidemiologist’, I constantly get asked what I do and what my (replace ‘my’ with ‘our’, as I do everything within a team) research can lead to. Please see my previous post ‘Searching for “Breathtaking” genes. Literally!‘ and My Research page for short answers to these questions. In tandem to these, I am constantly asked ‘why we can’t find a ‘cure’ for (noncommunicable) diseases that affect/will affect most of us such as obesity, diabetes, cancer, COPD – although there are many scientific advancements?’. I looked around for a straight forward example, but couldn’t find one (probably didn’t look hard enough!). So I decided to write my own.

I will first try and put the question into context: We do have ‘therapies’ and ‘preventive measures’ for most diseases and sometimes making that distinction from ‘a cure’ answers their question. For example, coronary heart disease (CHD) is a major cause of death both in the UK and worldwide (see NHS page for details) but we know how we can prevent many CHD cases (e.g. lowering cholesterol, stopping smoking, regular exercise) and treat CHD patients (e.g. statins, aspirin, ACE inhibitors). However, there are currently there are no ‘cures’ for CHD. So once a person is diagnosed with CHD, it is currently impossible to cure them from it, but doctors can offer quite a few options to make their life better.

I then gave it some thought about why finding a ‘cure’ was so hard for most diseases, and came up with the below analogy of a river/sea, water dam, and a nicely functioning village/city (excuse my awful drawing!).

The first figure below sets the scene: there’s a water dam that’s keeping the river from flooding and damaging the nice village/city next to it. Now please read the caption of the below figure to make sense of how they’re related to a disease.

Prevention

The river/sea is the combination of your genetic risk (e.g. you could have inherited genetic variants from your parents that increased your chances of type-2 diabetes) and environmental exposures (e.g. for type-2 diabetes, that would be being obese, eating high sugar content diet, smoking). The water dam is your immune system and/or mechanisms in your body which tame the sea of risk factors to ensure that everything in your body work fine (e.g. pancreatic islet cells have beta cells which produce insulin to lower your glucose levels back to normal levels – which would be damaging to the body’s organs if it stayed high).

So to ‘prevent’ a disease (well, flooding in this case), we could (i) make the water dam taller, (ii) make the dam stronger, and (iii) do regular checks to patch any damage done to the dam. To provide an example, for type-2 diabetes, point (i) could correspond to being ‘fit’ (or playing with your genes, which currently isn’t possible), point (ii) could correspond to staying ‘fit’, and point (iii) could correspond to having regular check-ups to see whether any preventive measures are necessary. Hope that made sense. If not, please stop reading immediately and look for other blog posts on the subject matter 🙂

Using the figure below, I wanted to then move to ‘therapy’. So as you can see, the river has flooded i.e. this individual has the disease (e.g. type-2 diabetes as above). The water dam is now not doing a good job of stopping the river and the city is in danger of being destroyed. But we have treatments: (i) The (badly drawn) water pumping trucks suck up excess water, and (ii) we have now built a second (smaller) dam to protect the houses and/or slow the flow of the water. Again, to provide an example using type-2 diabetes, water pumping trucks could be analogous to insulin or metformin injections, and the smaller dams could be changing current diet to a ‘low sugar’ version. This way we can alleviate the effects of the current and future ‘floods’.

Therapy

Analogy for therapy/treatment – after being diagnosed with the disease

Finally, we move on to our main question: ‘the cure’. Using the same analogy as above, as the water dam is now dysfunctional, the only way to stop future ‘floods’ would be to design a sewage system that can mop up all water that could come towards the city. Of course the water dam and ‘old city’ was destroyed/damaged due to past floods, so we’d need to build a new functioning city to take over the job of the old one. A related real example (off the top of my head) could be to remove the damaged tissues and replace them with new ones. Genetic engineering (using CRISPR/Cas9) and/or stem cell techniques are likely to offer useful options in the future.

Cure

Analogy for cure – after being diagnosed with the disease

Hopefully it is now clear that the measures taken to prevent or treat the disease, cannot be used to cure the disease. E.g. you can build another dam in place of the old one, but the city is already destroyed so that’s not going to be of any use in curing the disease.

So to sum up, diseases like obesity, cancer, COPD are very complex diseases – in fact they’re called ‘complex diseases’ in the literature – and understanding their underlying biology is very hard (e.g. hundreds of genes and environmental exposures could combine to cause them). We’re currently identifying many causal variants but turning these findings into ‘cures’ is a challenge that we have not been able to crack yet. However, it is clear that the methods that we currently use to identify preventive measures and therapies cannot be used to identify cures.

I hope that was helpful. I’d be very happy to read your comments/suggestions and share credit with contributing scientists. Thanks for reading!

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BBC_news_sperm_count

BBC news article published on the 18th March 2018. According to the article, men with low sperm counts are at a higher risk of disease/health problems. However, this is unlikely to be a causal relationship and more likely to be a spurious correlation. May even turn out to be the other way round due to “reverse causality”, a bias we encounter a lot in epidemiological studies. The following sounds more plausible (to me at least!): “Men with disease/health problems are likely to have low sperm counts” (likely cause: men with health problems tended to smoke more in general and this caused low sperm counts in those individuals).

As an enthusiastic genetic epidemiologist (keyword here: epidemiologist), I try to keep in touch with the latest developments in medicine and epidemiology. However, it is impossible to read all articles that come out as there is a lot of epidemiology and/or medicine papers published daily (in fact, too much!). For this reason, instead of reading the original academic papers (excluding papers in my specific field), I try to skim read from reputable news outlets such as the BBC, The Guardian and Medscape (mostly via Twitter). However, health news even in these respectable media outlets are full of wrong and/or oversensationalised titles: they either oversensationalise what the scientist has said or take the word of the scientist they contact – who are not infallible and can sometimes believe in their own hypotheses too much.

It wouldn’t harm us too much if the message of an astrophysics related publication is misinterpreted but we couldn’t say the same with health related news. Many people take these news articles as gospel truth and make lifestyle changes accordingly. Probably the best example for this is the Andrew Wakefield scandal in 1998 – where he claimed that the MMR vaccine caused autism and gastro-intestinal disease but later investigations showed that he had undeclared conflicts of interest and had faked most of the results (click here for a detailed article in the scandal). Many “anti-vaccination” (aka anti-vax) groups used his paper to strengthen their arguments and – although now retracted – the paper’s influence can still be felt today as many people, including my friends, do not allow their children to be vaccinated as they falsely think they might succumb to diseases like autism because of it.

The first thing we’re taught in our epidemiology course is “correlation does not mean causation.” However, a great deal of epidemiology papers published today report correlations (aka associations) without bringing in other lines of evidence to provide evidence for a causal relationship. Some of the “interesting ones” amongst these findings are then picked up by the media and we see a great deal of news articles with titles such as “coffee causes cancer” or “chocolate eaters are more successful in life”. There have been instances when I read the opposite in the same paper a couple of months later (example: wine drinking is protective/harmful for pregnant women). The problem isn’t caused only due to a lack of scientific method training on the media side, but also due to health scientists who are eager to make a name for themselves in the lay media without making sure that they have done everything they could to ensure that the message they’re giving is correct (e.g. triangulating using different methods). As a scientist who analyses a lot of genetic and phenotypic data, it is relatively easier for me to observe that the size of the data that we’re analysing has grown massively in the last 5-10 years. However, in general, we scientists haven’t been able to receive the computational and statistical training required to handle these ‘big data’. Today’s datasets are so massive that if we take the approach of “let’s analyse everything we got!”, we will find a tonne of correlations in our data whether they make sense or not.

To provide a simple example for illustrative purposes: let’s say that amongst the data we have in our hands, we also have each person’s coffee consumption and lung cancer diagnosis data. If we were to do a simple linear regression analysis between the two, we’d most probably find a positive correlation (i.e. increased coffee consumption means increased risk of lung cancer). 10 more scientists will identify the same correlation if they also get their hands on the same dataset; 3 of them will believe that the correlation is worthy of publication and submit a manuscript to a scientific journal; and one (other two are rejected) will make it past the “peer review” stage of the journal – and this will probably be picked up by a newspaper. Result: “coffee drinking causes lung cancer!”

However, there’s no causal relationship between coffee consumption and lung cancer (not that I know of anyway :D). The reason we find a positive correlation is because there is a third (confounding) factor that is associated with both of them: smoking. Since coffee drinkers smoke more in general and smoking causes lung cancer, if we do not control for smoking in our statistical model, we will find a correlation between coffee drinking and lung cancer. Unfortunately, it is not very easy to eliminate such spurious correlations, therefore health scientists must make sure they use several different methods to support their claims – and not try to publish everything they find (see “publish or perish” for an unfortunate pressure to publish more in scientific circles).

cikolata_ve_nobel_odulu

A figure showing the incredible correlation between countries’ annual per capita chocolate consumption and the number of Nobel laureates per 10 million population. Should we then give out chocolate in schools to ensure that the UK wins more Nobel prizes? However, this is likely not a causal relationship as it makes more sense that there is a (confounding) factor that is related to both of them: (most likely) GDP per capita at purchasing power parity. To view even quirkier correlations, I’d recommend this website (by Tyler Vigen). Image source: http://www.nejm.org/doi/full/10.1056/NEJMon1211064.

As a general rule, I keep repeating to friends: the more ‘interesting’ a ‘discovery’ sounds, the more likely it is to be false.

Hard to explain why I think like this but I’ll try: for a result to sound ‘interesting’ to me, it should be an unexpected finding as a result of a radical idea. There are just so many brilliant scientists today that finding unexpected things is becoming less and less likely – as almost every conceivable idea arises and is being tested in several groups around the world, especially in well researched areas such as cancer research. For this reason, the idea of a ‘discovery’ has changed from the days of Newtons and Einsteins. Today, ‘big discoveries’ (e.g. Mendel’s pea experimets, Einstein’s general relativity, Newton’s law of motion) have given way to incremental discoveries, which can be as valuable. So with each (well-designed) study, we’re getting closer and closer to cures/therapies or to a full understanding of underlying biology of diseases. There are still big discoveries made (e.g. CRISPR-Cas9 gene editing technique), but if they weren’t discovered by that respective group, they probably would have been discovered within a short space of time by another group as the discoverers built their research on a lot of other previously published papers. Before, elite scientists such as Newton and Einstein were generations ahead of their time and did most things on their own, but today, even the top scientists are probably not too ahead of a good postdoc as most science literature is out there for all to read in a timely manner (and more democratic compared to the not-so-distant past) and is advancing so fast that everyone is left behind – and we’re all dependent on each other to make discoveries. The days of lone wolves is virtually over as they will get left behind those who work in groups.

To conclude, without carefully reading the scientific paper that the newspaper article is referring to – hopefully they’ve included a link/citation at the bottom of the page! – or seeking what an impartial epidemiologist is saying about it, it’d be wise to take any health-related finding we read in newspapers with a pinch of salt as there are many things that can go wrong when looking for causal relationships – even scientists struggle to make the distinction between correlations and causal relationships.

power_posing

Amy Cuddy’s very famous ‘Power posing’ talk, which was the most watched video on the TED website for some time. In short, she states that if you give powerful/dominant looking poses, this will induce hormonal changes which will make you confident and relieve stress. However, subsequent studies showed that her ‘finding’ could not be replicated and she that did not analyse her data in the manner expected of a scientist. If a respectable scientist had found such a result, they would have tried to replicate their results; at least would have followed it up with studies which bring other lines of concrete evidence. What does she do? Write a book about it by bringing in anecdotal evidence at best and give a TED talk as if it’s all proven – as becoming famous (by any means necessary) is the ultimate aim for many people; and many academics are no different. Details can be found here. TED talk URL: https://www.ted.com/talks/amy_cuddy_your_body_language_shapes_who_you_are

PS: For readers interested in reading a bit more, I’d like to add a few more sentences. We should apply the below four criteria – as much as we can – to any health news that we read:

(i) Is it evidence based? (e.g. supported by a clinical trial, different experiments) – homeopathy is a bad example in this regard as they’re not supported by clinical trials, hence the name “alternative medicine” (not saying they’re all ineffective and further research is always required but most are very likely to be);

(ii) Does it make sense epidemiologically? (e.g. the example mentioned above i.e. the correlation observed between coffee consumption and lung cancer due to smoking);

(iii) Does it make sense biologically? (e.g. if gene “X” causes eye cancer but the gene is only expressed in the pancreatic cells, then we’ve most probably found the wrong gene)

(iv) Does it make sense statistically? (e.g. was the correct data quality control protocol and statistical method used? See figure below for a data quality problem and how it can cause a spurious correlation in a simple linear regression analysis)

graph-3

Wrong use of a statistical (linear regression) model. If we were to ignore the outlier data point at the top right of the plot, it becomes easy to see that there is no correlation between the two variables on the X and Y axes. However, since this outlier data point has been left in and a linear regression model has been used, the model identifies a positive correlation between the two variables – we would not have seen that this was a spurious correlation had we not visualised the data.

PPS: I’d recommend reading “Bad Science” by Ben Goldacre and/or “How to Read a Paper – The basics of evidence based medicine” by Trisha Greenhalgh – or if you’d like to read a much better article on this subject with a bit more technical jargon, have a look this highly influential paper by Prof. John Ioannidis: Why Most Published Research Findings Are False.

References:

Wakefield et al, 1998. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet. URL: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2897%2911096-0/abstract

Editorial, 2011. Wakefield’s article linking MMR vaccine and autism was fraudulent. BMJ. URL: http://www.bmj.com/content/342/bmj.c7452

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Autozplotter_mesut_erzurumluoglu

An example output from AutoZplotter using whole-exome sequencing data – used to identify the Primary ciliary dyskinesia causal gene, CCDC151, in Alsaadi and Erzurumluoglu et al, 2014 (read this paper’s story here). The green and red dots correspond to heterozygous and homozygous calls (for the alternative allele), respectively. The continuous blue lines correspond to the probability that the observed sequence of genotypes is not autozygous (e.g. close to zero means likely to be an autozygous region). LRoH: Long runs of homozygosity. NB: This image has been edited to ensure confidentiality/anonymity of the participant. Some LRoHs have been shortened or extended for this reason. If you’re thinking of using an AutoZplotter image in a paper, do not share genome-wide figures but maybe consider using chromosome-wide ones

When analysing whole-exome or whole-genome sequencing (or dense SNP chip) data obtained from consanguineous individuals with a rare Mendelian disease, the disease causal mutation usually lies within an autozygous region (characterised by long runs of homozygosity, LRoH, which are generally >5Mb). Thus checking whether any candidate genes overlap with an LRoH can substantially narrow region(s) of interest. There are several tools which can identify LRoHs such as Plink, AutoSNPa and AgilentVariantMapper. However, they all require their own formats and considerable computational knowledge; and also struggle to identify regions that are shorter than 5Mb. Thus, we wrote AutoZplotter, a user-friendly python script which plots the heterozygosity/homozygosity status of variants in a VCF file to allow for quick visualisation and manual identification of regions that have longer stretches of homozygosity than would be expected by chance.

VCF_format_v4

AutoZplotter accepts the VCF format – which is the standard format for storing genetic variation data from NGS platforms. Image Source URL: bioinf.comav.upv.es

The input format of AutoZplotter is VCF, thus it will be suitable for any type of genetic data (e.g. SNP array, WES, WGS) and from any species.

An older version of AutoZplotter was used in the analysis stage of Alsaadi et al (2012) and Alsaadi and Erzurumluoglu et al (2014).

To download latest version of AutoZplotter, click here (directs to ResearchGate). If you found AutoZplotter helpful in anyway, please cite Erzurumluoglu AM et al, 2015.

 

References:

Erzurumluoglu AM et al, 2015. Identifying Highly Penetrant Disease Causal Mutations Using Next Generation Sequencing: Guide to Whole Process. BioMed Research International. Volume 2015 (2015), Article ID 923491

Alsaadi MM and Erzurumluoglu AM et al, 2014. Nonsense Mutation in Coiled-Coil Domain Containing 151 Gene (CCDC151) Causes Primary Ciliary Dyskinesia. Human Mutation. Volume 35, Issue 12. Pages 1446–1448

Erzurumluoglu AM et al, 2016. Importance of Genetic Studies in Consanguineous Populations for the Characterization of Novel Human Gene Functions. Volume 80, Issue 3. Pages 187–196

Erzurumluoglu AM, 2015. Population and family based studies of Consanguinity: Genetic and Computational approaches. PhD Thesis. University of Bristol

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Laws regarding first-cousin marriage around the world. Navy blue: First-cousin marriage legal. Light Blue: Allowed with restrictions or exceptions. Yellow: Legality dependent on religion or culture. Red: Statute bans first-cousin marriage. Pink: Banned with exceptions. Dark Red: Criminal offense. Grey: No available data. The image has been released into the public domain by the author (URL: http://en.wikipedia.org/wiki/Cousin_marriage).

Laws regarding first-cousin marriage around the world. Navy blue: First-cousin marriage legal. Light Blue: Allowed with restrictions or exceptions. Yellow: Legality dependent on religion or culture. Red: Statute bans first-cousin marriage. Pink: Banned with exceptions. Dark Red: Criminal offense. Grey: No available data. The image has been released into the public domain by the author (URL: http://en.wikipedia.org/wiki/Cousin_marriage).

The answer is (studying) consanguinity (i.e. unions between relatives such as first-cousin marriages); and one cannot understand the complexity of the issue (and make ‘informed’ decisions) without reading the literature of these five apparently unconnected fields. It is fair to say that there is a degree of hostility towards consanguineous marriages in Western societies. However this perception is usually attained without in-depth knowledge on the genetic effects of consanguinity. In short, consanguinity per se (i.e. on its own) does not cause a disorder, but rather it increases the probability of an autosomal recessive disorder (which require two copies of the same) causal mutation to be in a homozygous state (i.e. possess two copies of the same mutation). When this happens both copies of the genes we inherited from our parents do not function properly.

Unions between individuals who are second-cousins or closer are considered ‘consanguineous’ in clinical genetics. Consanguineous families with diseases have been studied thoroughly by clinical geneticists for the last two-three decades – and this has allowed for identification of many disease causal genes. However, studying consanguineous populations as a whole rather than ‘cherry picking’ families with disease can offer much more for better understanding our genome and therefore finding new targets for preventive and curative medicine. Many genes in our genome still have unknown functions and we have merely scratched the surface in terms of their interactions. I hypothesise that assigning a function to the thousands of remaining genes will only be feasible if consanguineous populations are studied as a whole (i.e. also including families without disease to the studies) and I therefore carry out theoretical studies to estimate the sample size needed and how many genes will be completely ‘knocked-out’ if these studies were to be carried out. This approach proposes a ‘paradigm shift’ in clinical genetics.

Global prevalence of consanguineous unions. Consanguinity has deep roots in many cultures and it is impossible to interfere/intervene from the outside without first understanding why people engage in cousin marriages. Image source URL: www.consang.net/

Global prevalence of consanguineous unions. Consanguinity has deep roots in many cultures and it is impossible to interfere/intervene from the outside without first understanding why people engage in cousin marriages. Image source URL: http://www.consang.net/

Consanguineous unions occur very rarely in Western countries for a variety of sociological (e.g. cultural, negative media coverage) and statistical reasons (e.g. smaller families means fewer cousins at similar age), but the complete opposite is true in certain regions of the world where union of kin is seen as the default choice. Conservative estimates predict that approximately one-sixth of the world’s population (a figure of 1.1 billion is proposed by the Geneva International Consanguinity Workshop Report) live in highly consanguineous regions; and also another one-sixth falls into the ‘unknown’ category – reflecting the need for further research. Historically, consanguineous unions were also common amongst the elite in the UK (up to mid-19th century, including Charles Darwin), the Pharaohs and the Royal families of Europe (e.g. Habsburgs).

Views of main religions towards consanguineous marriages. NB: Where first-cousin marriages are allowed, lower levels of consanguinity are also allowed. Image Source: Copy-pasted from my own PhD thesis

The increase in the probability of a mutation being homozygous will depend on the level of relatedness between the parents. For example, approximately 6.25% of mutations are expected to be homozygous in the offspring of first cousins. This figure would be (near) 0% in the offspring of outbred individuals. Genetically, this is the main difference between union of kin and union of unrelated individuals. We all have many disease-causal mutations in our genomes (but in heterozygous state, i.e. one normal copy and one mutated copy) and different kinds of mutations are out there in all populations. However because these mutations will be very rare or are unique to you or your family, they do not get to meet their counterpart when you have offspring with an unrelated individual. Therefore the mutation’s homozygous effects are never observed. This is why rare autosomal recessive disorders are almost always seen in consanguineous offspring.

This difference in homozygosity levels is also one of the main reasons behind the necessity of studying consanguineous individuals and populations. These studies can turn unfortunate events (e.g. disorder in families) to a great use for medical sciences. Not only will identifying a disease-causal mutation help with diagnostics, they can enable scientists to understand what certain genes do and help us understand why the gene causes that disease. Rare instances can be highly informative about preventable outcomes relevant to the whole population. For example, had more notice been taken in the 1980s of the proof which familial hypercholesterolemia provided for the causal role of cholesterol in coronary heart disease (CHD), high cholesterol intake would have been better addressed for the nation a decade sooner. To provide numbers, CHD is still the UK’s biggest killer causing over 80 thousand deaths a year, thus paying more attention to information that was coming from studies of consanguineous unions could have saved thousands of lives just in this single case.

Given the advancements in genetic diagnostics (e.g. huge decreases in costs of DNA sequencing), screening for all known mutations will become feasible in the near future for everybody – and identifying disease-causal mutations will become even more useful for all of us. Our genomes are constantly being mutated and my approach will enable a much broader understanding of our genome by observing these mutations’ homozygous effects. Finally, rather than discourage (See link for an example) consanguineous marriages totally (not feasible in the foreseeable future due to many socio-economic and cultural reasons), for those willing to marry a cousin, screening for previously identified mutations will help these couples take more informed decisions.

consanguinity factors culture socio-economic

Factors influenced by consanguinity and culture. Image Source: Copy-pasted from my own PhD thesis (hence the Figure 1.10)

Key reference:

A. Mesut Erzurumluoglu, 2016. Population and family based studies of consanguinity: Genetic and Computational approaches. PhD thesis. University of Bristol.

Erzurumluoglu AM et al, 2016. Importance of Genetic Studies in Consanguineous Populations for the Characterization of Novel Human Gene Functions. Annals of Human Genetics, 80: 187–196.

 

PS: Whilst the media is mostly responsible for portraying consanguinity the way they understand (and with more contrast added on of course), they could be forgiven as the genetic effects of consanguinity is not fully understood amongst geneticists either, especially in the field of complex trait genetics – thus the extra incentive for studying them.

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Obesity is a big problem World-wide

Obesity is a ‘big fat’ problem World-wide (Image from Wikipedia)

Obesity increases the risk of a variety of disorders such as coronary heart disease (UK’s biggest killer!) and cancer (e.g. colon, breast) and influences other health related traits such as increasing blood pressure and blood fats. Therefore it is always important to know what your normal range for body mass index (BMI) is. Keeping within this range is bound to decrease your risk for obesity related disorders – although should not be solely relied on. Intake of right amount of minerals and vitamins is also crucial.

The NHS have created an online BMI calculator which I found very useful:

BMI healthy weight calculator

 

PS: Please also check the BMI of your loved ones (especially elder members) as most people usually ignore the early signs and become obese… Warn them if they’re overweight so that it is easier to lose weight compared to when they’re already obese!

PPS: There is also some useful and succinct info on this website

content provided by NHS Choices

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Our eyes have been blurred with distractions
Our eyes have become blurred with distractions. We lost touch with the realities of this life.
Note: Scroll down for the English version of this post

Hayatın anlamını araştıran/sorgulayanların çoğu zaman, dinleri ve Allah’ı tamamen yalanlayanlardan olmasını anlamıyorum; gerçekten anlamıyorum!

Soylemeliyim ki hiçbir zaman bulamayacaksınız; egonuzu (nefsinizi) yenip/dizginleyip, Hakk’ın (c.c.) önünde eğilmediginiz surece! Biraz sert bir cevap gibi gelebilir ama gerçek bu. Samimiyetle O(c.c.)’nu bulmak istersek, ben Allah’ın bize ‘doğru yol’u gosterecegine inanıyorum. Buna siz de inanın!

Shakespeare, Tolstoy, Dostoyevsky, Dickens, Orwell’i okumak/anlamak için harcadıgımız zamanın onda birini Allah’ı (şimdilik varlıgına inanın ya da inanmayın) tanımaya/anlamaya harcasak da ondan sonra kararımızı versek.

Bir köpek dahi sahibini tanıyorsa, insan kendisini yaratandan geleni hayli hayli tanır. Kendi tecrübemden konuşuyorum. Kuran’a bakın; ve size (herkesinki farklı) tesir edecek öyle ayetler karşınıza çıkacak ki “işte bu kitap beni Yaratan’dan gelmiş!” dedirtecek!


Ek: İşe nasıl bir mucize ve ne kadar önemli birisi oldugunu tefekkür ederek başlayabilirsin. Ben de (beni etkileyen) bir örnekle yardımcı olmaya çalışayım: Mesela senin gibi bir insan dünya tarihinde olmadı; olmayacak! Eşsiz bir insansın! Allah seni (evet sadece seni!) yaratmak için annenle babanı tanıştırdı ve kalplerini birbirlerine ısıttı. Annenin 300 küsür yumurtasının arasında, babanın da milyarlarca spermi arasında seni yaratacak kombinasyonu seçti. Aynı şey, anne-baban ve dede-ninelerin için de gecerli… Onların anne-babası için de… Onlardan önceki nesiller içinde… Bu halkada bir tane eksik veya degişim olsaydı, sen olmayacaktın!

Ek 2: Arzu ederseniz ‘Evrim teorisi‘ (ingilizce) ve ‘hayat gayem‘le ilgili yazdıgım eski yazılarıma da göz gezdirebilirsiniz…

rumi_mevlana

People who’ve asked me “what is the meaning of life?” had one thing in common: Outright denial of all religions and (any idea of a) God

This is what I can’t understand; I really can’t!

Most of the time, any answer I gave would be thrown back at me with distaste. Sorry but – as a friend whose willing to help you – I’ll tell you what I believe and try backing them up with as much evidence (which convinces me) as possible, but it is up to you to be convinced or not. I don’t have the power to tune anybody’s heart or mind…

For me: Without religion, there’s no* meaning to life! Otherwise life just becomes: “You live because you were born; you had no choice!”

“Life was just an accident and your sperm happens to be the (un)lucky one out of the zillions that your father produced – also the same applies to your father; and his father… You just have to put up with it.”

Having no sense of meaning in life is why many people who have no belief in God and the afterlife commit suicide or waste their life (e.g. drugs, night life, gambling, games); and the one’s who don’t, live in constant fear of death – especially when they get older…

There can only be one “true” religion in the world – others will have no, some or a lot of truth in it but can’t be the “true religion”; and everybody has to make it their primary aim to find it! We spend hours reading Orwell, Shakespeare, Tolstoy, Dostoevsky’s works (rightly so! they can teach us a lot) but rarely do we look at the books which have (trying to word it as an objective person) “supposedly” been sent to us by God himself. Why aren’t we curious about them? How many of them have we read?

The true religion has to answer all reasonable philosophical questions which come to mind, whilst not contradicting scientific and historical facts… Also this doesn’t mean that we must “like” the answers that are given. Truth almost always hurts.

I believe I’ve found it and it has stood the test of time, however what convinces me may not convince you/others. Therefore everyone’s on their own conquest to find the truth and the true religion – the thing that will give our lives a meaning.

Please see my post God of Science for a few arguments on the existence of God (and the wrong belief that current scientific knowledge in genetics is incompatible with God). Happy to discuss any points…

*Read Albert Camus and other ‘existentialist’ philosophers (e.g. Sartre, Nietzsche) if you don’t believe me – they were atheists and believed that life had no meaning, so try(!) enjoying it while lasts…

Rumi-Quote-Ways-to-Jannah
There are as many ways to Paradise as there are human souls – Rumi

PS: There is a school of thought which believes that we’re made up of life, soul and body. Thus as long as we’re alive, the soul is tied to the body (via life). This can explain why we become unconscious (and ‘blackout’) when we faint. However when we die, we will not be unconscious as the ‘tie’ that is life (as we understand it) does not exist anymore. Thus the soul is free to travel (and get rid of the shackles/limitations of the body) and meet the Creator. Please read around the idea if interested. Happy to discuss…

PPS: I respect everyone’s beliefs – and lack of it. It is their own life choice at the end of the day! However it would selfish of me not to share/propagate something that I believe is to be true (i.e. belief in the existence of an omniscient and omnipotent God).

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