Familial aggregation

A disease whose pattern of familial aggregation differs from that expected fi om the Mendelian inheritance of a single genetic defect. 

I The occurrence of MDD shows a familial pattern because first-degree relatives of MDD patients are about three times more likely to develop MDD compared with first-degree relatives of normal control individuals. Adoption studies and twin studies reveal that the familial aggregation of MDD is due to genetic influences.5... 

Both genetic and nongenetic factors play roles in the transmission of mood disorders. The familial nature of mood disorders is well established. Studies over the past 20 years have consistently documented higher rates of mood disorder in the relatives of individuals with major depression and bipolar disorder than in relatives of healthy controls [6,7], The familial aggregation of mood disorders is the outcome of both genetic and environmental factors. 

Breitner, J.C.S., Silverman, J.M., Mohs, R.C., Davis, K.L. (1988) Familial aggregation in Alzheimer s disease comparison of risk among relatives of early-and late-onset cases, and among male and female relatives in successive generations. Neurology, 38, 207-212. 

The familial aggregation of all of the major subtypes of anxiety disorders has been well-established (Merikangas and Herrell 2004). As reviewed in the following section, when taken together, the results of more than a dozen controlled family studies of probands with specific subtypes of anxiety disorders demonstrate a three- to five-fold elevated risk of anxiety disorders among first-degree relatives of affected probands compared to those of controls. The... 

There is also evidence for both the familial aggregation and heritability of generalized anxiety disorder (GAD) in a limited number of studies. There is a five-fold average increase in the rister of GAD among relatives of probands with GAD compared to that among relatives of controls 5 (Mendlewicz et al. 1993 Noyes et al. 1987) and the heritability of GAD among female twins is 0.32 (Kendler et al. 1992). 

There are also very few controlled family studies of obsessive-compulsive disorder. Two of the three studies (Pauls et al. 1995) reported familial relative risks of 3-4, whereas a third study (Black et al. 1992) found no evidence for familial aggregation. Nestadt et al. (2000) found that both an early age of onset and obsessions, but not compulsion were associated with greater familiality. Twin studies have yielded weak evidence for heritability of obsessive-compulsive disorder (Bellodi et al. 1992 Carey and Gottesman 1981 Lenane et al. 1990). 

Goldstein RB, Wickramaratne PJ, Horwath E, Weissman MM (1997) Familial aggregation and phenomenology of early -onset (at or before age 20 years) panic disorder. Arch Gen Psychiatry 54 271-278... 

Merikangas KR, Stevens DE, Fenton B, Stolar M, O Malley S, Woods SW, Risch N (1998b) Co-morbidity and familial aggregation of alcoholism and anxiety disorders. Psychol Med 28 773-788... 

Kendler KS, Davis CG, Kessler RC (1997) The familial aggregation of common psychiatric and substance use disorders in the National Comorbidity Survey a family history study. Br J Psychiatry 170 541-548... 

Although of much less clinical relevance, it must be emphasized that certain disturbances of HDL metabolism cause familial aggregation of elevated HDL cholesterol... 

Goes FS, Zandi PP, Miao K, McMahon FJ, Steele J, et al. 2007. Mood-incongruent psychotic features in bipolar disorder Familial aggregation and suggestive linkage to 2pll-ql4 and 13q21-33. Am J Psychiatry 164 236-247. 

Clemen-Stone, S. (2002). Defining community health nursing. In S. Clemen-Stone, S. L. McGuire, D. G. Eigsti, eds. Comprehensive community health nursing Family, aggregate, and community practice (6th ed., pp. 30-51). St. Louis Mosby. 

Isolated instances of familial aggregation of PBC involving siblings, twins, mother and daughter or father and daughter have been reported. The occurrence of AMA as well as an increase in IgM and y-GT, or deficiency of IgA has been observed in relatives of PBC patients (genetics close physical contact ). It is not a hereditary disease, however. (59, 66, 83, 85, 87, 89, 90, 117, 127, 144, 148, 163, 275)... 

Ebers GC, Sadovnick AD, Risch NJ (1995) A genetic basis for familial aggregation in multiple sclerosis. Canadian collaborative study group. Nature 377 150-151. 

Bulimia nervosa shows marked family aggregation. This is thought to be due to environmental factors interacting with genetic predisposition (see below). 

Increased cholesterol is a factor in the cause of atherosclerotic diseases (see also Chapter 44). As early as 1910, Windaus described cholesterol in the lesions of diseased arteries. Subsequently, many studies have confirmed that free and esterified cholesterol accumulates in the aorta, coronary arteries, and cerebral vessels, and that the rate of accumulation varies among individuals. The association between serum cholesterol and atherosclerosis in humans was first suggested in 1938, when Muller and Thanhauser each demonstrated familial aggregation of hypercholesterolemia... 

Sniderman A, Teng B, Genest J, Cianflone K, Wacholder S, Kwiterovich P, Jr. Familial aggregation and early expression of hyperapobetalipoproteinemia. Am J Cardiol 1985 55 291-5. 

Buskila D, Neumann L, Hazanov I, et al. Familial aggregation in the fibromyalgia syndrome. Semin Arthritis Rheum 1996 26(3) 6O5-1L... 

Ellison, R.C., Myers, R.H., Zhang, Y., Djousse, L, Knox, S., Williams, R. R., and Province, M.A. Effects of similarities in lifestyle habits on familial aggregation of high density lipoprotein and low density lipoprotein cholesterol the NHLBl Family Heart Study. Am. J. Epidemiol., 1999, 350, 910-918. 

---