Familial Aggregation and Heritability of Schizophrenia and Co-aggregation of Psychiatric Illnesses in Affected Families

Abstract

Strong familial aggregation of schizophrenia has been reported but there is uncertainty concerning the degree of genetic contribution to the phenotypic variance of the disease. This study aimed to examine the familial aggregation and heritability of schizophrenia, and the relative risks (RRs) of other psychiatric diseases, in relatives of people with schizophrenia using the Taiwan National Health Insurance Database. The study population included individuals with affected first-degree or second-degree relatives identified from all beneficiaries (n = 23 422 955) registered in 2013. Diagnoses of schizophrenia made by psychiatrists were ascertained between January 1, 1996 and December 31, 2013. Having an affected co-twin, first-degree relative, second-degree relative, or spouse was associated with an adjusted RR (95% CI) of 37.86 (30.55–46.92), 6.30 (6.09–6.53), 2.44 (1.91–3.12), and 1.88 (1.64–2.15), respectively. Compared with the general population, individuals with one affected first-degree relative had a RR (95% CI) of 6.00 (5.79–6.22) and those with 2 or more had a RR (95% CI) of 14.66 (13.00–16.53) for schizophrenia. The accountability for the phenotypic variance of schizophrenia was 47.3% for genetic factors, 15.5% for shared environmental factors, and 37.2% for non-shared environmental factors. The RR (95% CI) in individuals with a first-degree relative with schizophrenia was 3.49 (3.34–3.64) for mood disorders and 3.91 (3.35–4.57) for delusional disorders. A family history of schizophrenia is therefore associated with a higher risk of developing schizophrenia, mood disorders, and delusional disorders. Heritability and environmental factors each account for half of the phenotypic variance of schizophrenia.

Thought Disorder in Schizophrenia and Bipolar Disorder Probands, Their Relatives, and Nonpsychiatric Controls

“…6,[47][48][49][50][51][52][53][54][55][56][57][58][59][60] This nonspecificity is also consistent with the substantial (but incomplete 61,62 ) overlap in genetic susceptibility loci across psychiatric disorders [63][64][65][66][67][68][69][70] and with recent work documenting that the familial aggregation of psychiatric disorders is much less specific than had been thought. [71][72][73][74][75][76][77] Both Kraepelin and Bleuler observed that the biological family members of SZ patients often displayed what appeared to be attenuated SZ traits (eg, odd speech), and concluded that the psychopathology of SZ was not limited to the psychotic form of the illness. Bleuler referred to such states as latent SZ, which he considered to be a "diluted" form of the illness that included the central feature of "loosening of associations."…”

Schizophrenia and the neurodevelopmental continuum:evidence from genomics

“…In recent years, there has been increasing evidence from family studies for shared, as well as independent, genetic risk between different adult psychiatric disorders, and between adult disorders and childhood neurodevelopmental disorders. There has also been an accumulation of evidence that schizophrenia shares environmental risk factors with childhood neurodevelopmental disorders, particularly those likely to index early neurodevelopmental impairment.…”

S.16.02 Schizophrenia and the neurodevelopmental continuum; new support from genomics

“…In recent years, there has been increasing evidence from family studies for shared, as well as independent, genetic risk between different adult psychiatric disorders, and between adult disorders and childhood neurodevelopmental disorders 7,[13][14][15][16] . There has also been an accumulation of evidence that schizophrenia shares environmental risk factors with childhood neurodevelopmental disorders, particularly those likely to index early neurodevelopmental impairment [17][18][19][20][21] .…”