Observational methods for human studies of transgenerational effects

Figures & data

Table 1. Proband-centric transgenerational relationship classification.

Ancestor exposed	Ahnentafel Numbering System	Intergenerational	Transgenerational
Proband with phenotype		n/a	n/a
Parent
Father	XM	Yes	No
Mother	XF	Yes	No
Grandparent
Paternal Grandfather	XMM	Potential	Yes
Paternal Grandmother	XMF	Potential	Yes
Maternal Grandfather	XFM	Yes	Potential
Maternal Grandmother	XFF	Yes	Potential
Great Grandparent
Paternal Great Grandparents	XMMM, XMMF, XMFM, XMFM	Potential	Yes
Maternal Great Grandparents	XFMM, XFMF, XFFM, XFFF	Potential	Yes

Figure 1. Space-time clusters of paternal ancestors of children diagnosed with ASD, 1996–2018, in Utah, USA.

Table 2. Crude odds ratios for grandparent living within 5 km of an active smelter, by type of grandparent and time period.

Exposure window	Exposure period	# total	# case	# controls	% cases exposed	% cntl exposed	cOR	LCL	UCL	p-value
Paternal Grandfather
Birth	All	4487	1683	2804	0.13	0.14	0.90	0.77	1.10	0.353
	<1950	2360	834	1526	0.15	0.14	1.03	0.81	1.31	0.800
	≥1950	2127	849	1278	0.11	0.13	0.81	0.62	1.06	0.132
Childhood	All	4676	1468	3208	0.13	0.14	0.94	0.78	1.13	0.499
	<1950	2087	661	1426	0.15	0.16	0.93	0.72	1.20	0.576
	≥1950	2589	807	1782	0.12	0.12	0.94	0.73	1.22	0.664
Puberty	All	1657	521	1136	0.14	0.15	0.94	0.68	1.26	0.692
	<1950	489	158	331	0.15	0.18	0.75	0.45	1.27	0.290
	≥1950	1,168	363	805	0.14	0.14	1.05	0.73	1.49	0.807
Paternal Grandmother
Birth	All	4345	1454	2891	0.47	0.46	1.03	0.90	1.17	0.682
	<1950	1973	661	1312	0.62	0.60	1.11	0.92	1.35	0.284
	≥1950	2372	793	1579	0.34	0.35	0.96	0.80	1.15	0.660
Childhood	All	4547	1487	3060	0.45	0.43	1.08	0.95	1.23	0.230
	<1950	1691	548	1143	0.57	0.51	1.25	1.09	1.54	0.032
	≥1950	2856	939	1917	0.38	0.38	0.99	0.85	1.17	0.931
Puberty	All	2409	681	1368	0.43	0.40	1.11	0.91	1.34	0.288
	<1950	364	121	243	0.53	0.47	1.25	0.81	1.93	0.317
	≥1950	1685	560	1125	0.41	0.57	0.51	0.42	0.62	<0.001

Data availability statement

The data that supports our research are available from the UPDB and URADD after permission from the Utah Department of Health, University of Utah IRB, and the Utah Resource for Genetic and Epidemiologic Research and are not publicly available. Given the sensitivity of the data content, the data cannot be obtained without the above-mentioned approvals. However, the authors, specifically the communicating authors, invite any and all communication pertaining to the data and are happy to present the data in a setting where the oversight committees have granted permission.