Marriage between first cousins increases the prevalence of neurological birth defects by about 100%, with this excess attributable to increased autosomal recessive causes (23, 24), and with de novo chromosome anomalies representing a correspondingly reduced portion of the total (24). Although comparable epidemiological data for autism are not available, we reasoned that a prominent involvement of autosomal recessive genes in autism would be signaled by differences in the male-to-female (M/F) ratio of affected children in consanguineous (related) versus nonconsanguineous marriages (although recessive causes of autism may still retain some gender-specific difference in penetrance). Across the HMCA, the M/F ratio of affected individuals was typical, at 4.8:1 (115 males: 24 females). However, in consanguineous, multiplex pedigrees, the M/F ratio was 2.6:1 (34 males: 13 females) (fig. S1), compared to 7.4:1 (81 males: 11 females) for the other categories of families (i.e., nonconsanguineous and consanguineous simplex) (chi-square = 5.37, df = 1, P = 0.02). The M/F ratio of 2.6:1 is close to what would be predicted if the prevalence of autism were doubled in these families, with the excess attributable to recessive causes (23, 24).
