CDRF | FACTFILE

LAY DEFINITION
A common bone disease causing thin bones leading to fractures of the hip, wrist and spine which leads to progressive bending of the spine and so called Dowagers hump.
MEDICAL DEFINITION
A disease of bone characterized by low bone mass and micro-architectural deterioration, leading to enhanced bone fragility and an increased risk of fracture. Defined by the WHO as an individual with a bone density result (using a DEXA scan) less than 2.5 standard deviations below the mean level of a 30 year-old individual.
SIZE OF THE PROBLEM
One in three women and one in eight men will suffer an osteoporotic fracture in their lifetime, mainly hip, spine and wrist fractures, and the numbers are increasing every year, due to the ageing population. It has been estimated to cost the US in excess of 9 billion dollars annually and 1 billion pounds in the UK.
ROLE OF GENETIC FACTORS
Family history is important. Having a first degree relative (e.g. parent or sister) with a hip fracture increases your risk two-fold, and a wrist or Colles fracture 3 fold. Twin studies have estimated that approximately 75% of the variability of bone density is due to genetic factors (heritability). Other risk factors for fracture are also under genetic influence; bone structure (60%), bone turnover (50-70%), age of menopause (60%), muscle strength (50%), bone size (60%).
GENES INVOLVED
A number of different genes are likely to be involved in osteoporosis. No gene has yet been proven beyond doubt to be involved in humans, but leading contenders include; vitamin D receptor gene, collagen type 1 gene, oestrogen receptor gene and transforming growth factor beta gene.
GENETIC TESTS
No commercially available tests are in use at present.

LAY DEFINITION
A form of arthritis involving joint destruction and swelling, causing pain and handicap believed to be caused by the body attacking the cells in the joints.
MEDICAL DEFINITION
A symmetrical autoimmune inflammatory polyarthritis causing swelling and destruction of the synovium with particular predilection for the small joints of the hand, wrist and feet. Can later affect larger joints and also lead to secondary OA changes.
SIZE OF THE PROBLEM
Affects about 1% of the population, being twice as common in women. It can occur at any age but increases with age, commonly occurring between 30 and 60. Although less common than osteoarthritis, it is more severe and a much greater percentage of patients are severely disabled by it and require joint replacement surgery. Patients have an increased mortality due to infections and other causes.
ROLE OF GENETIC FACTORS
Family history is important. Having a first degree relative (e.g. parent or sister) with RA increases your risk approximately three fold. Twin studies have estimated the proportion of disease variance explained by genetic factors (heritability) to be around -60%.
GENES INVOLVED
A number of different genes are likely to be involved in RA. The genes of the MHC region on chromosome 6 controlling the HLA system, particularly HLA DR4 and DR-1 may account for 25% of the gene effect. Patients with these HLA gene markers have an approximate 4-8 fold increased risk of severe disease, although the association with mild disease is less strong. Other genes under investigation are those controlling the major cytokines IL-1 and IL-6 and others.
GENETIC TESTS
Although the HLA test will suggest an increased risk, it is not used clinically or commercially as the frequency of the HLA type is too high in the normal population.

LAY DEFINITION
The commonest form of arthritis involving a wearing out of cartilage and bone around joints, causing pain, stiffness and loss of function.
MEDICAL DEFINITION
A group of diseases affecting different body sites involving loss or destruction of cartilage, bony reaction and sclerosis and variable amounts of inflammation. Commonly affects the fingers, thumbs, knees, hips and spine, and can also appear as a generalized form affecting all joints
SIZE OF THE PROBLEM
One in two people over the age of 55 will have some degree of osteoarthritis (OA), about 1 in 6 will seek medical attention. It costs the USA alone about $100 billion in medical costs and lost productivity. In the UK about 50,000 joint replacements are carried out annually and about 300,000 in the US. For most sites except the hip it is commoner in females. The risk of OA increases with age and obesity is a major risk factor, particularly for the knee. Other environmental risk factors are previous joint injuries and joint surgery.
ROLE OF GENETIC FACTORS
Family history is important. Having a first degree relative (e.g. parent or sister) with OA increases your risk two-three fold. Twin studies have estimated the proportion explained by genetic factors (heritability) varies from 50-60% for the hand, knee , hip and spine. Bony swellings on the ends of the fingers are called Heberden’s’ nodes. These may also be genetic and tend to run in families in females and are a sign of increased risk of large joint problems later in life. The genetic component may be different between men and women.
GENES INVOLVED
A number of different genes are likely to be involved in osteoarthritis; some may be similar to those influencing the bone disease osteoarthritis. No gene has yet been proven to be involved in humans, but leading contenders include; collagen II and collagen IX genes, vitamin D receptor gene and transforming growth factor beta gene.
GENETIC TESTS
No commercially available tests are in use at present.

LAY DEFINITION
Pain in the lower back due to muscular, disc or arthritis problems. May be associated with sciatica, which is related pain down the back of the leg often associated with a disc problem.
MEDICAL DEFINITION
No universally accepted definition of back pain is available. Common uses for research are pain in the lower back for more than 1 month that causes disability. Back pain is caused by a complex combination of muscular, anatomical, arthritic, neurogenic and psychological factors. Disc disease is said to be present when there is evidence of degeneration or prolapse of the inter-vertebral discs.
SIZE OF THE PROBLEM
Back pain affects up to 60% of the population at some time in their lives. Up to 20% have severe back pain causing disability lasting more than 1 month. In most episodes the pain resolves in less than 6 weeks, although 1% of patients may have severe disc disease warranting surgery. The frequency increases with age, peaking in middle-age, but new episodes are rare over the age of 65. Back pain is one of the commonest causes of lost working hours in western countries and has a huge economic and social burden. Known risk factors include smoking, tall stature and some occupations. Depression and anxiety are also important risk factors.
ROLE OF GENETIC FACTORS
Family history has been shown to be important, with a two-fold risk in first degree relatives. Recent twin studies from St Thomas’ have shown that lumbar disc disease using magnetic resonance imaging has a heritability of around 60%. Back pain itself not related to disc changes may also be heritable, suggesting that muscular and ligament problems as well as pain tolerance may be under genetic control. These suggest that genetic factors are more important than environmental or lifestyle effects.
GENES INVOLVED
The main genes that have been studied are those for osteoarthritis, namely unconfirmed reports of vitamin D receptor gene and transforming growth factor beta gene. Little work has been performed in large samples and it is likely that there are more important genes awaiting discovery.
GENETIC TESTS
none available.

LAY DEFINITION
A recurrent throbbing headache that characteristically affects one side of the head. The attack may be preceded by a warning, such as flickering lights or blurred vision. Is often associated with nausea and vomiting and light avoidance.
MEDICAL DEFINITION
A paroxysmal disorder with headaches, often unilateral at onset, associated with nausea, anorexia, and often vomiting; it is preceded or accompanied by visual, sensory, motor or mood disturbances.
SIZE OF THE PROBLEM
Migraine is common, affecting up to 33% of women and 13% of men over a lifetime. In one year this affects 25% of women and 7% of men. There is a wide spectrum of severity and half of all sufferers never seek medical attention. It can also occur in children below the age of 10, but most cases occur between 18-65. 65% of cases never have a classical aura. Aetiological factors include hormones, (pregnancy improves it and the pill worsens it) stress and anxiety, food intolerance and exercise. The prevalence of migraine was significantly higher in women and not associated with socio-economic status. They suffered a median of 12 migraine attacks per year; 25% had at least two attacks per month.
ROLE OF GENETIC FACTORS
Migraine has a strong genetic component. In a large Danish twin study, the probandwise concordance rate was higher in MZ than DZ twin pairs (0.43 versus 0.31;).. The estimated heritability is around 60% with the remaining effects, being due to non-shared environmental factors. The risk in 1st degree relatives is 2-3 fold. Both types of migraine (with and without aura) appear to be similarly genetic as does the disease in men and women. MZ twins reared apart had similar concordances to those reared together. The interest in a genetic basis for the disorder has increased after identification of three genetic loci for familial hemiplegic migraine (FHM), which is a rare subtype with autosomal dominant inheritance.
GENES INVOLVED
The dopamine D2 receptor (DRD2) and allelic variation of the human serotonin transporter gene (HSERT), have been proposed as candidate genes in common migraine, and the rare familial form FHM has been linked to Ch 19p13. Genes may differ for migraine with and without aura.
GENETIC TESTS
None available

LAY DEFINITION
Also known as juvenile diabetes, because the disease mostly presents itself around puberty. The disease is characterized by the fact that the pancreas is no longer capable of producing insulin, which means sugars cannot produce energy in the body. Symptoms are thirst, weight loss and fatigues and excessive production of urine. This makes administration of this essential hormone in these patients necessary.
MEDICAL DEFINITION
Another name type I diabetes, a so called auto-immune disease in which the insulin producing beta-cells of the Islets of Langerhans in the pancreas are destroyed by the own immune system. In practice often defined by the need for insulin injections. Can also be defined as the abnormal response to an oral glucose load.
SIZE OF THE PROBLEM
It has a frequency of 1 in 100-200. Primary complications of IDDM are due to blood glucose values that are too high (hyperglycaemia). Sometimes treatment can cause levels to be too low (hypoglycaemia). Secondary complications can be serious and include damage to the vessels of the retina of the eye (retinopathy), the kidneys (nephropathy), heart and arteries (vasculopathy) and the nervous system (neuropathy). Often starts in puberty and most of the mortality and morbidity are long term.
ROLE OF GENETIC FACTORS
Genetic factors are assumed to play an important role in IDDM, probably by interacting with environmental factors. Risk to an individual with a first-degree family member with the disease is 6%, whereas the risk in non-diabetes families is only 0.3%, an increased risk of 18-fold.
GENES INVOLVED
A number of different genes are likely to be involved in IDDM. Just like for many other auto-immune diseases, there is evidence that the genes coding for the part of the immune system that is involved in recognition of ‘self’ and ‘non-self’ (the class II region of the Human Leukocyte Antigen system) are involved. In addition, the promotor of the insulin gene itself if likely to be involved.
GENETIC TESTS
The HLA test is not discriminatory enough to be useful as a clinical test at present.

LAY DEFINITION
Also known as type 2 diabetes or maturity onset diabetes. It is associated with having too much sugar in the blood due to the body’s natural insulin failing to work properly. It is associated with putting on weight. As opposed to IDDM the disease mostly presents itself at an older age (usually > 45 years), and is more common but with less severe consequences.
MEDICAL DEFINITION
The disease is characterized by high blood glucose levels that might go undetected for years. The disease is thought to be due to a combination of reduced sensitivity to insulin of glucose uptaking cells and an impairment of insulin secretion by the pancreatic beta-cells. It is associated with the syndrome of insulin resistance, characterized by high cholesterol, hypertension, hyperglycaemia, and central obesity.
SIZE OF THE PROBLEM
In the westernized world 4-10% of people suffer from NIDDM. Prevalence of NIDDM varies widely in different ethnic groups and for example in the UK is higher in blacks and south-asians.
ROLE OF GENETIC FACTORS
Besides genetic factors, being overweight is a very important risk factor for the development of NIDDM. The risk in first degree relatives is about 2-4 fold. Twin studies suggest a heritability of around 50-70%. A variant of IDDM is maturity onset diabetes of the young (MODY) which is characterized by an early age of onset and autosomal dominant inheritance. MODY is not an uncommon disorder and in fact could account for about 2 to 5% of all cases of type 2 diabetes.
GENES INVOLVED
A number of different genes are likely to be involved in NIDDM, suggestions include the insulin gene, IGF-1, MODY gene, although none has been unequivocally confirmed. There is some evidence for parental imprinting, with fathers determining the likely hood of diabetes in offspring rather than mothers. Recent studies have shown that mutations in four transcription factors, 3 hepatocyte factors and insulin promoter factor-1 (IPF-1) are largely responsible for the variant MODY.
GENETIC TESTS
None available

LAY DEFINITION
Being overweight is a common problem in the westernized world. Someone becomes overweight when for a prolonged period energy intake (what you eat and drink) exceeds energy output (the energy you use in everyday activities).
MEDICAL DEFINITION
According to the WHO an adult is overweight if the Body Mass Index exceeds 25 kg/m2. Body Mass Index (BMI) is defined as weight in kilograms over height in meters squared. Someone suffers from obesity if he/she is seriously overweight, which is defined as a BMI > 30kg/m2. The global epidemic of obesity results from a combination of genetic susceptibility, increased availability of high-energy foods and decreased requirement for physical activity in modern society
SIZE OF THE PROBLEM
Up to 50% of the adult population are overweight, whereas up to 10% are seriously overweight, being greater in countries such as the US. Rates are steadily increasing. Obesity is now so common within the world's population that it is beginning to replace under-nutrition and infectious diseases as the most significant contributor to ill health. In particular, obesity is associated with diabetes mellitus, coronary heart disease, osteoarthritis, back pain, certain forms of cancer, and sleep-breathing disorders.
ROLE OF GENETIC FACTORS
Genetic factors are very important and heritabilities for BMI range between 50 and 80%. Where fat is deposited (and therefore body shape) is also under genetic control with a heritability of around 60%
GENES INVOLVED
After the location of the OB gene in mice in 1996 and the discovery of its product called leptin it was initially thought that the development of a fat pill was not far off. However, these expectations have proved far too optimistic with weight regulation in humans being much more complicated than in mice. Other genes implicated include the UCP3, agouti genes and beta 3 adrenergic genes.
GENETIC TESTS
Not available

LAY DEFINITION
Raised blood pressure leading to increased risk of heart disease and strokes.
MEDICAL DEFINITION
The problem is to define ‘raised’, as blood pressure rises with age. Many studies suggest a level greater than 160/90 mm Hg should arbitrarily be used. Readings should be taken on a number of occasions. However the risk is a continuous one and different criteria should be applied in the young or elderly depending on the risks and benefits of treatment
SIZE OF THE PROBLEM
Hypertension itself is not really a disease, but its consequences are. It causes a several fold increase in heart disease and strokes and increases the thickness of heart muscle and alters the properties of blood vessels. Its prevalence depends on the definition or cutoff used, ranging from 2% in 20 year olds to 50% in the over 70’s
ROLE OF GENETIC FACTORS
Blood pressure is influenced by environmental (diet, exercise, weight) and genetic factors. As blood pressure is highly variable estimates of heritability depend on how carefully it was measured and vary from 25-70%, the highest being for 24hour recordings. Other measures of ‘central blood pressure’ such as augmentation index, a measure of vessel elasticity are also genetic with heritabilities of around 40%. Blood pressure is higher in children of hypertensive parents.
GENES INVOLVED
The principal genes have been those of the renin-angiotensin system. Furthermore, the coding and regulatory regions of the genes encoding for renin, ACE, angiotensinogen and the AT1 receptor have been partially characterized.
GENETIC TESTS
Not available

LAY DEFINITION
A disease leading to wheezing and shortness of breath
MEDICAL DEFINITION
Reversible airways obstruction associated with wheezing and shortness of breath. Often defined using lung function tests, which show a response to bronchodilators such as ventolin.SIZE OF THE PROBLEM
The frequency depends on the definition. As many as one in three young children have episodes of wheezing. The prevalence of asthma in children is about 10% and in adults is around 5%, and accounts for about 50,000 hospital admissions and around 2000 deaths annually. The rates of asthma in most countries are increasing. It is associated with a group of atopic diseases including an increased frequency of hay fever, and eczema.
ROLE OF GENETIC FACTORS
Asthma has both environmental and genetic influences and is affected by allergens and dust. Asthma runs in families with the risk in 1st degree relatives being approximately 4 fold. The risk is also increased if parents have any atopic diseases. Twins studies have shown heritabilities of between 30-60% for most of the different definitions. The risk may vary from the mothers or fathers genes.
GENES INVOLVED
There are likely to be common atopy genes that determine susceptibility to asthma, hay fever and eczema. Cytokine and growth factor genes (e.g. IL-1, IL-4,6) have been implicated , but no clear candidates have emerged, partly because of difficulties in definition and diagnosis.
GENETIC TESTS
Not available.

LAY DEFINITION
Disease of the lungs causing shortness of breath, cough and sometimes sputum, often associated with smoking.
MEDICAL DEFINITION
Obstruction of the small and medium sized pulmonary airways also known as reversible or partly reversible airways obstruction. Commonly divided into 3 types, partly reversible (asthma type discussed elsewhere), emphysema type (where distal air spaces are destroyed) and bronchial (chronic bronchitis) where small airways are narrowed and there is excess sputum production. Chronic bronchitis can also be defined as the presence of a cough productive of sputum for more than 3 months a year in two consecutive years.
SIZE OF THE PROBLEM
Accounts for about 6% of all male deaths and causes about 100,000 deaths per annum in the UK alone. Chronic bronchitis has a prevalence of around 15% in populations over 50, is commoner in men and about four times more common in smokers, although most smokers do not develop the disease. Levels may be declining slightly.
ROLE OF GENETIC FACTORS
Little work has been performed in this area to date, and estimates are very approximate although the disease is believed to run in families. Cigarette smoke, containing reactive oxygen species, is the most important risk factor and genes probably interact in smokers and in the presence of other environmental factors to produce the disease. Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung.
GENES INVOLVED
The only established genetic risk factor for COPD is homozygosity for the Z allele of the alpha1-antitrypsin gene. Heterozygotes for the Z allele may also be at increased risk. Other mutations affecting the structure of alpha1-antitrypsin or the regulation of gene expression have been identified as possible risk factors. Genes, including those for alpha1-antichymotrypsin, alpha2-macroglobulin, vitamin D-binding protein and blood group antigens, have also been associated with the development of COPD. Variants of the cystic fibrosis transmembrane regulator gene have been identified as risk factors for disseminated bronchiectasis
GENETIC TESTS
Alpha 1-Antitrypsin (AAT) deficiency, is a rare disease (1 in 5000 people) caused by genetically determined AAT deficiency. It occurs as a result of inheritance of two protease inhibitor (PI) deficiency alleles from the AAT gene locus (designated PI) on chromosomal segment 14q32.1. There are genetic tests for this in research centres but it accounts for only a small proportion of chronic lung disease.

LAY DEFINITION
Heart disease leading to angina or heart attacks which can be fatal.
MEDICAL DEFINITION
Also known as Ischaemic heart disease, caused by a combination of factors, including atheroma of the major arteries and clogging of the vessels with thrombus and inflammation of the vessels. The end result is myocardial infarction or angina. It can also be asymptomatic.
SIZE OF THE PROBLEM
The commonest cause of death in developed countries causing approximately a third of deaths in males, and is one of the commonest causes of early death in males, loss of employment years and disability. Rates have started to decrease in many countries since a peak in the 1970’s. This may be due to changes in diet. In men up to 15% have angina or ECG changes in middle-age.
ROLE OF GENETIC FACTORS
Whilst smoking, obesity and diet are important risk factors there is also an important genetic factor. In a study of twins among the men, the relative risk of death from coronary heart disease when one's twin died of coronary heart disease before the age of 55 was 8 for monozygotic twins and 4 for dizygotic twins. Among the women, when one's twin died of coronary heart disease before the age of 65 years, the relative risk was 15.0 for monozygotic twins and 2.6 for dizygotic twins. The genetic effect appears to decrease at older ages. This translates to a 3-4 fold increase in 1st degree relatives. The reasons for this risk are probably the individual risks of inheriting the risk factors, such as lipids with heritability of 40-70%, clotting factors (40-75%), obesity (60-70%) etc.
GENES INVOLVED
There are no known genes that explain heart disease per se, although a number of candidate genes for the risk factors, such as those influencing low density lipoproteins, apoE and apoB have been associated with increased risk for cardiovascular disease morbidity or mortality.
GENETIC TESTS
Only available for rare diseases of familial lipid or cholesterol disorders.

LAY DEFINITION
A mental state of excessive sadness
MEDICAL DEFINITION
Persistent flattening of mood accompanied by biological features (diurnal variation, anorexia, weight loss, early waking, loss of libido, thought retardation, poor self-image). It is probably not a discrete entity, but a continuous trait with individuals with the full range in the community. Often diagnosed in research used structured questionnaires.
SIZE OF THE PROBLEM
It is a major cause of suicide, accounting for about 5000 deaths a year in the UK. About 5-10% of the population can be defined as being depressed at any one time depending on the definition. It is more common in women, varies in symptoms with race, is common in single status or divorced individuals and is also affected by external life events.
ROLE OF GENETIC FACTORS
Twin studies have shown heritabilities in women of 30-50%, with an additional component related to shared environment. There is a substantial shared genetic component with the genes controlling neuroticism. The risk in 1st degree relatives is around 2-4 fold. Post-natal depression also has a genetic component with a heritability of around 40%.
GENES INVOLVED
No confirmed genes have yet been identified
GENETIC TESTS
Not available.

LAY DEFINITION
Eczema is also a very common skin disease well known to the public. It is characterized by red and itchy patches most commonly found on the arms and legs and is very common in childhood and usually resolve in adulthood
MEDICAL DEFINITION
Eczema is a form of allergy and is associated with other atopic disorders such as asthma, hay fever and rhinitis. It is characterized by erythematous, scaly and sometimes weepy lesions on the flexor surfaces of the arms and legs. Eczema peaks in childhood with most cases improving into adulthood. It can be exacerbated by stress. When severe it can involve the entire body, which will often necessitate hospital admission.
SIZE OF THE PROBLEM
The prevalence of eczema is high in childhood reaching up to 25% in population based studies. Almost 80% of childhood eczema resolves by adulthood.
GENETIC BASIS
It appears that the genetic of eczema is very complex and environmental factors also play an important role. Family studies have shown clustering and other atopic disorders such as asthma, rhinitis (hay fever) also co-segregate in atopic families. Twin studies have shown that 30 to 70% of the susceptibility to eczema may be attributed to genetic factors.
GENES INVOLVED
A few genes have been implicated in eczema (chromosome 5q31, 11q13, 14q11.2 and 16p12) but eczema is likely to be a complex polygenic diseases and so far no major genes for this disease have been discovered.
GENETIC TESTING
There are currently no genetic testing which can predict if an individual may be susceptible to atopic disorders.

LAY DEFINITION
Psoriasis is not so well known but when a family member suffer from it, it is usually well recognized as psoriasis is characterized by typical flaky and red plaques most often found on the elbows, knees and scalp. It is rare in childhood but can occur at any age.
MEDICAL DEFINITION
Psoriasis is characterized by an abnormal proliferation of the skin cells called keratinocytes with infiltration by lymphocytes and this defect forms thick red and scaly plaques which can occur anywhere on the body but usually affect the knees, elbows, sacrum and scalp. Psoriasis can also be associated with joint symptoms due to psoriatic arthritis, which can be very incapacitating and involves about 5% of cases of psoriasis. Psoriasis usually affects adults and is seen in all ethnic groups. When generalized, it can be a severe condition, which may need admission to hospital.
SIZE OF THE PROBLEM
Psoriasis affects up to 3% of the population and appears to be exacerbated by stress, alcohol and smoking and some medications such as beta-blockers.
GENETIC BASIS
It has long been suspected that psoriasis is a genetic disease and many family studies have already been set up for gene discovery. In identical twins, psoriasis is also more concordant in identical twins with a concordance of 60% compared to 20% in non identical twins but the expression of the disease does vary through life so family and twin studies may underestimate the real prevalence of the disease. The risk of psoriasis to a first degree relative of an affected subject is between15 to 25%, or a 6-7 fold increased risk.
GENES INVOLVED
As many as 10 areas of the genome have been linked to psoriasis but no gene has so far been identified. The linkage to chromosome 6p in the HLA region has been confirmed by many studies and different HLA subtypes are associated with psoriasis depending on age of onset. Research suggests that psoriasis is likely to be influenced by different genes with a complex mode of inheritance.
GENETIC TESTING
There are no genetic tests for psoriasis currently available.

LAY DEFINITION
The reason people require spectacles or glasses to improve their eyesight, usually one of short sight (unable to see in distance clearly), long sight (difficulty reading near) and astigmatism (blurred vision for all tasks).
MEDICAL DEFINITION
Myopia usually occurs due to excessive growth of the axial length of the eye, resulting in focus of parallel rays of light in front of the retina, and is corrected with a concave (minus power) lens. Hypermetropia occurs when light is focussed behind the retina and is due to a short eye or a flattened cornea which focuses light less well than a normally curved cornea, and is corrected with convex (magnifying) lenses. Astigmatism causes light to be focussed in two places due to the cornea having a different radius of curvature in two different planes rather than a symmetrical round curvature, and is corrected with cylindrical corrective lenses.
SIZE OF THE PROBLEM
Refractive errors are extremely common in the population, with a huge economic impact all over the world. Myopia affects over 40% of the middle-aged population in the west, and is becoming increasingly common, particularly in areas such as the far east where 90% of university undergraduates are myopic. Uncorrected refractive errors are an important cause of poor vision both in the elderly in the west and in all age groups in developing countries. Hypermetropia affects over 40% of the population and astigmatism affects around a third.
ROLE OF GENETIC FACTORS
Family studies have shown a significant risk of myopic parents producing myopic children with odds ratios of up to 5-fold. There has been little work on hypermetropia and astigmatism. Twin studies have shown myopia and hypermetropia to be highly genetic, with heritabilities up to 85%. The heritability of astigmatism was 50% in one twin study, and may be dominantly inherited.
GENES INVOLVED
There have now been two genes identified in familial high myopia, in families with severe myopia and pathological retinal changes associated, but no genes isolated for the more common forms of myopia. No genes have been identified for hypermetropia and astigmatism.
GENETIC TESTS
Not available.

LAY DEFINITION
Cloudiness in the lens of the eye affecting elderly people, which results in blurred vision and requires a cataract operation to restore vision.
MEDICAL DEFINITION
The three main forms of age-related cataract or opacification of the lens affect different regions of the lens: nuclear cataract, the commonest reason for cataract surgery, cortical cataract and posterior subcapsular cataract, particularly associated with diabetes and steroid use. Early stages may induce myopia or cause symptoms of glare, but more advanced cataract reduces visual acuity and requires cataract extraction with intraocular lens implant.
SIZE OF THE PROBLEM
Some degree of cataract is almost inevitable with advancing age, and cataract extraction is the commonest operation in the world, with over 1.5 million surgeries performed in the United States every year. Cataract is the commonest cause of world blindness, and the WHO estimates cataract is responsible for 25 million blind people in the world.
ROLE OF GENETIC FACTORS
There has been little research into genetic factors of cataract, but one family study estimated a major gene could account for up to 35% of nuclear cataract and up to 58% of the variability of cortical cataract. A twin study has estimated the heritability of nuclear cataract at 48% and of cortical cataract at 53-58%.
GENES INVOLVED
Expression of the homeobox gene SIX5 has been identified in the mature lens but not the fetal lens, and a mutation has been implicated in adult onset cataract associated with myotonic dystrophy. However there have been no genetic mutations found in isolated age-related cataract to date.
GENETIC TESTS
Not available.

LAY DEFINITION
A disease of the retina (the light sensitive area that lines the inside of the eye) affecting elderly people that causes either gradual or sudden loss of central vision.
MEDICAL DEFINITION
Age-related macular degeneration is characterized the presence of drusen and other abnormalities of the retinal pigment epithelium in the macular area of the retina, and may lead to gradual loss of central vision (geographic atrophy or dry changes) or neovascularization from the choroid breaking through into the subretinal area causing haemorrhage and fibrosis which results in sudden loss of vision (exudative or wet macular degeneration, resulting in a disciform scar).
SIZE OF THE PROBLEM
Macular degeneration is by far the commonest cause of blindness in developed countries, and is increasingly common as the population ages. Projected estimates for the UK indicate that by the year 2020 as many as 7.5 million persons in the over-65 age group may suffer from visual loss due to macular degeneration. Over 10% of people over the age of 80 have visual loss due to this condition.
ROLE OF GENETIC FACTORS
Family studies have suggested a high relative risk in relatives of those with late age-related macular degeneration, with a prevalence up to 20 times compared to those without a family history. More recent studies have suggested it may be a small minority of families who have high genetic risk. Twin studies have shown concordance of late changes of around 90% in monozygotic twins.
GENES INVOLVED
Several hereditary retinal dystrophies show similarities to macular degeneration and these genes are potential candidate susceptibility genes. Particular interest has focused on the ABCR gene which is responsible for autosomal recessive Stargardt macular dystrophy. It has been claimed that heterozygotes for ABCR mutations are predisposed to macular degeneration but the data are conflicting. Studies of other genes for retinal dystrophies have been negative. Recent data suggest that the ApoE _4 allele may be associated with a reduced risk of disease, and in one large family, linkage has been reported to markers in 1q25-q31.
GENETIC TESTS
Not available.